The SCF/c-KIT system in the male: Survival strategies in fertility and cancer

Molecular Reproduction and Development

Volumn 81, Issue 12, 2014, Pages 1064-1079

  Cardoso, Henrique J ^a   Figueira, Marília I ^a   Correia, Sara ^a   Vaz, Cátia V ^a   Socorro, Sílvia ^a  

^a UNIVERSITY OF BEIRA INTERIOR   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

ISOPROTEIN; STEM CELL FACTOR; STEM CELL FACTOR RECEPTOR;

APOPTOSIS; CELL DIFFERENTIATION; CELL FATE; CELL PROLIFERATION; CELL SURVIVAL; GERM CELL; HUMAN; INTRACELLULAR SIGNALING; MALE FERTILITY; MALE INFERTILITY; MEIOSIS; NONHUMAN; ONCOGENE C KIT; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TARGETING; REVIEW; SPERMATOGENESIS; STEROIDOGENESIS; TESTIS CANCER; UPREGULATION; BIOLOGICAL MODEL; CELL CYCLE; FERTILITY; GENETICS; GENITAL SYSTEM; MALE; METABOLISM; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

CELL CYCLE; CELL DIFFERENTIATION; FERTILITY; GENITALIA; HUMANS; MALE; MODELS, BIOLOGICAL; NEOPLASMS; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS C-KIT; SIGNAL TRANSDUCTION; STEM CELL FACTOR;

EID: 84920051800     PISSN: 1040452X     EISSN: 10982795     Source Type: Journal    
DOI: 10.1002/mrd.22430     Document Type: Review

References (166)

1. Advani AS. 2005. C-kit as a target in the treatment of acute myelogenous leukemia. Curr Hematol Rep 4:51-58.
2. Albanesi C, Geremia R, Giorgio M, Dolci S, Sette C, Rossi P. 1996. A cell- and developmental stage-specific promoter drives the expression of a truncated c-kit protein during mouse spermatid elongation. Development 122:1291-1302.
3. Ali S, Ali S. 2007. Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST). Gene 401:38-45.
4. Ali S, Ravindranath N, Jia MC, Musto N, Tsujimura T, Kitamura Y, Dym M. 1996. Expression of multiple c-kit receptor messenger ribonucleic acid transcripts during postnatal development of the rat testis. Biochem Biophys Res Commun 218:104-112.
5. Arber DA, Tamayo R, Weiss LM. 1998. Paraffin section detection of the c-kit gene product (CD117) in human tissues: Value in the diagnosis of mast cell disorders. Hum Pathol 29:498-504.
6. Bajaj GK, Zhang Z, Garrett-Mayer E, Drew R, Sinibaldi V, Pili R, Denmeade SR, Carducci MA, Eisenberger MA, Deweese TL. 2007. Phase II study of imatinib mesylate in patients with prostate cancer with evidence of biochemical relapse after definitive radical retropubic prostatectomy or radiotherapy. Urology 69:526-531.
7. Biermann K, Goke F, Nettersheim D, Eckert D, Zhou H, Kahl P, Gashaw I, Schorle H, Buttner R. 2007. c-KIT is frequently mutated in bilateral germ cell tumours and down-regulated during progression from intratubular germ cell neoplasia to seminoma. J Pathol 213:311-318.
8. Blechman JM, Lev S, Givol D, Yarden Y. 1993. Structure-function analyses of the kit receptor for the steel factor. Stem Cells 11:12-21.
9. Blechman JM, Lev S, Barg J, Eisenstein M, Vaks B, Vogel Z, Givol D, Yarden Y. 1995. The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction. Cell 80:103-113.
10. Blume-Jensen P, Hunter T. 2001. Oncogenic kinase signalling. Nature 411:355-365.
11. Blume-Jensen P, Janknecht R, Hunter T. 1998. The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol 8:779-782.
12. Blume-Jensen P, Jiang G, Hyman R, Lee KF, O'gorman S, Hunter T. 2000. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3'-kinase is essential for male fertility. Nat Genet 24:157-162.
13. Bokemeyer C, Kuczyk MA, Dunn T, Serth J, Hartmann K, Jonasson J, Pietsch T, Jonas U, Schmoll HJ. 1996. Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours. J Cancer Res Clin Oncol 122:301-306.
14. Broudy VC, Kovach NL, Bennett LG, Lin N, Jacobsen FW, Kidd PG. 1994. Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor. Blood 83:2145-2152.
15. Caruana G, Cambareri AC, Ashman LK. 1999. Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts. Oncogene 18:5573-5581.
16. Ceder JA, Jansson L, Ehrnstrom RA, Ronnstrand L, Abrahamsson PA. 2008. The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate. Eur Urol 53:524-531.
17. Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. 1988. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335:88-89.
18. Choudhury A, Zhao H, Jalali F, Al Rashid S, Ran J, Supiot S, Kiltie AE, Bristow RG. 2009. Targeting homologous recombination using imatinib results in enhanced tumor cell chemosensitivity and radiosensitivity. Mol Cancer Ther 8:203-213.
19. Claesson-Welsh L. 1994. Platelet-derived growth factor receptor signals. J Biol Chem 269:32023-32026.
20. Correia S, Alves MR, Cavaco JE, Oliveira PF, Socorro S. 2014. Estrogenic regulation of testicular expression of stem cell factor and c-kit: Implications in germ cell survival and male fertility. Fertil Steril 102:299-306.
21. Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE. 1993. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood 82:1151-1158.
22. Dahlen DD, Lin NL, Liu YC, Broudy VC. 2001. Soluble Kit receptor blocks stem cell factor bioactivity in vitro. Leuk Res 25:413-421.
23. D'auriol L, Mattei MG, Andre C, Galibert F. 1988. Localization of the human c-kit protooncogene on the q11-q12 region of chromosome 4. Hum Genet 78:374-376.
24. De Felici M, Dolci S. 2013. Preface. Male germ cells and cancer: A connection among pluripotency, differentiation and stem cell biology. Int J Dev Biol 57:101-103.
25. De Miguel MP, Cheng L, Holland EC, Federspiel MJ, Donovan PJ. 2002. Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer. Proc Natl Acad Sci USA 99:10458-10463.
26. Deberry C, Mou S, Linnekin D. 1997. Stat1 associates with c-kit and is activated in response to stem cell factor. Biochem J 327:73-80.
27. Derry JJ, Prins GS, Ray V, Tyner AL. 2003. Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene 22:4212-4220.
28. Dirami G, Ravindranath N, Pursel V, Dym M. 1999. Effects of stem cell factor and granulocyte macrophage-colony stimulating factor on survival of porcine type A spermatogonia cultured in KSOM. Biol Reprod 61:225-230.
29. Dogan S, Mason MC, Govindaraju A, Belser L, Kaya A, Stokes J, Rowe D, Memili E. 2013. Interrelationships between apoptosis and fertility in bull sperm. J Reprod Dev 59:18-26.
30. Dolci S, Pellegrini M, Di Agostino S, Geremia R, Rossi P. 2001. Signaling through extracellular signal-regulated kinase is required for spermatogonial proliferative response to stem cell factor. J Biol Chem 276:40225-40233.
31. Dym M, Jia MC, Dirami G, Price JM, Rabin SJ, Mocchetti I, Ravindranath N. 1995. Expression of c-kit receptor and its autophosphorylation in immature rat type A spermatogonia. Biol Reprod 52:8-19.
32. El-Agamy DS. 2012. Targeting c-kit in the therapy of mast cell disorders: Current update. Eur J Pharmacol 690:1-3.
33. Farini D, La Sala G, Tedesco M, De Felici M. 2007 Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells. Dev Biol. 306:572-583.
34. Feng H, Sandlow JI, Sandra A. 1997. Expression and function of the c-kit proto-oncogene protein in mouse sperm. Biol Reprod 57:194-203.
35. Feng HL, Sandlow JI, Sparks AE, Sandra A, Zheng LJ. 1999. Decreased expression of the c-kit receptor is associated with increased apoptosis in subfertile human testes. Fertil Steril 71:85-89.
36. Feng LX, Ravindranath N, Dym M. 2000. Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia. J Biol Chem 275:25572-25576.
37. Flanagan JG, Chan DC, Leder P. 1991. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell 64:1025-1035.
38. Fox RA, Sigman M, Boekelheide K. 2000. Transmembrane versus soluble stem cell factor expression in human testis. J Androl 21:579-585.
39. Fukuda T, Hedinger C, Groscurth P. 1975. Ultrastructure of developing germ cells in the fetal human testis. Cell Tissue Res 161:55-70.
40. Gagari E, Rand MK, Tayari L, Vastardis H, Sharma P, Hauschka PV, Damoulis PD. 2006. Expression of stem cell factor and its receptor, c-kit, in human oral mesenchymal cells. Eur J Oral Sci 114:409-415.
41. Gaskell TL, Esnal A, Robinson LL, Anderson RA, Saunders PT. 2004. Immunohistochemical profiling of germ cells within the human fetal testis: Identification of three subpopulations. Biol Reprod 71:2012-2021.
42. Ge RS, Dong Q, Sottas CM, Papadopoulos V, Zirkin BR, Hardy MP. 2006. In search of rat stem Leydig cells: Identification, isolation, and lineage-specific development. Proc Natl Acad Sci USA 103:2719-2724.
43. Geissler EN, Ryan MA, Housman DE. 1988. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 55:185-192.
44. Geissler EN, Liao M, Brook JD, Martin FH, Zsebo KM, Housman DE, Galli SJ. 1991. Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter. Somat Cell Mol Genet 17:207-214.
45. Gommerman JL, Sittaro D, Klebasz NZ, Williams DA, Berger SA. 2000. Differential stimulation of c-Kit mutants by membrane-bound and soluble Steel Factor correlates with leukemic potential. Blood 96:3734-3742.
46. Grootegoed JA, Siep M, Baarends WM. 2000. Molecular and cellular mechanisms in spermatogenesis. Baillieres Best Pract Res Clin Endocrinol Metab 14:331-343.
47. Guerif F, Cadoret V, Rahal-Perola V, Lansac J, Bernex F, Panthier JJ, Hochereau-De Reviers MT, Royere D. 2002. Apoptosis, onset and maintenance of spermatogenesis: Evidence for the involvement of Kit in Kit-haplodeficient mice. Biol Reprod 67:70-79.
48. Hakovirta H, Yan W, Kaleva M, Zhang F, Vanttinen K, Morris PL, Soder M, Parvinen M, Toppari J. 1999. Function of stem cell factor as a survival factor of spermatogonia and localization of messenger ribonucleic acid in the rat seminiferous epithelium. Endocrinology 140:1492-1498.
49. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144:646-674.
50. Hayashi S, Kunisada T, Ogawa M, Yamaguchi K, Nishikawa S. 1991. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res 19:1267-1271.
51. Hersmus R, Stoop H, Van De Geijn GJ, Eini R, Biermann K, Oosterhuis JW, Dhooge C, Schneider DT, Meijssen IC, Dinjens WN, Dubbink HJ, Drop SL, Looijenga LH. 2012. Prevalence of c-KIT mutations in gonadoblastoma and dysgerminomas of patients with disorders of sex development (DSD) and ovarian dysgerminomas. PLoS ONE 7:e43952.
52. Hess RA, Renato De Franca L. 2008. Spermatogenesis and cycle of the seminiferous epithelium. Adv Exp Med Biol 636:1-15.
53. Hofer MD, Fecko A, Shen R, Setlur SR, Pienta KG, Tomlins SA, Chinnaiyan AM, Rubin MA. 2004. Expression of the platelet-derived growth factor receptor in prostate cancer and treatment implications with tyrosine kinase inhibitors. Neoplasia 6:503-512.
54. Huang EJ, Nocka KH, Buck J, Besmer P. 1992. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell 3:349-362.
55. Imura M, Kojima Y, Kubota Y, Hamakawa T, Yasui T, Sasaki S, Hayashi Y, Kohri K. 2012. Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia. Prostate 72:1506-1513.
56. Izadyar F, Wong J, Maki C, Pacchiarotti J, Ramos T, Howerton K, Yuen C, Greilach S, Zhao HH, Chow M, Chow YC, Rao J, Barritt J, Bar-Chama N, Copperman A. 2011. Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod 26:1296-1306.
57. Izquierdo MA, Van Der Valk P, Van Ark-Otte J, Rubio G, Germa-Lluch JR, Ueda R, Scheper RJ, Takahashi T, Giaccone G. 1995. Differential expression of the c-kit proto-oncogene in germ cell tumours. J Pathol 177:253-258.
58. Jackson CM, Jackson H. 1984. Comparative protective actions of gonadotrophins and testosterone against the antispermatogenic action of ethane dimethanesulphonate. J Reprod Fertil 71:393-401.
59. Kapur R, Chandra S, Cooper R, Mccarthy J, Williams DA. 2002. Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor. Blood 100:1287-1293.
60. Kemmer K, Corless CL, Fletcher JA, Mcgreevey L, Haley A, Griffith D, Cummings OW, Wait C, Town A, Heinrich MC. 2004. KIT mutations are common in testicular seminomas. Am J Pathol 164:305-313.
61. Kierszenbaum AL, Rivkin E, Tres LL. 2007. Molecular biology of sperm head shaping. Soc Reprod Fertil Suppl 65:33-43.
62. Kimura Y, Inoue K, Abe M, Nearman J, Baranowska-Kortylewicz J. 2007. PDGFRbeta and HIF-1alpha inhibition with imatinib and radioimmunotherapy of experimental prostate cancer. Cancer Biol Ther 6:1763-1772.
63. Kissel H, Timokhina I, Hardy MP, Rothschild G, Tajima Y, Soares V, Angeles M, Whitlow SR, Manova K, Besmer P. 2000. Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses. EMBO J 19:1312-1326.
64. Kubler HR, Van Randenborgh H, Treiber U, Wutzler S, Battistel C, Lehmer A, Wagenpfeil S, Hartung R, Paul R. 2005. In vitro cytotoxic effects of imatinib in combination with anticancer drugs in human prostate cancer cell lines. Prostate 63:385-394.
65. Lammie A, Drobnjak M, Gerald W, Saad A, Cote R, Cordon-Cardo C. 1994. Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem 42:1417-1425.
66. Langley KE, Mendiaz EA, Liu N, Narhi LO, Zeni L, Parseghian CM, Clogston CL, Leslie I, Pope JA, Lu HS, Zsebo KM, Boone TC. 1994. Properties of variant forms of human stem cell factor recombinantly expressed in Escherichia coli. Arch Biochem Biophys 311:55-61.
67. Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J. 1997. Kit receptor dimerization is driven by bivalent binding of stem cell factor. J Biol Chem 272:6311-6317.
68. Lennartsson J, Ronnstrand L. 2012. Stem cell factor receptor/c-Kit: From basic science to clinical implications. Physiol Rev 92:1619-1649.
69. Lennartsson J, Blume-Jensen P, Hermanson M, Ponten E, Carlberg M, Ronnstrand L. 1999. Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction. Oncogene 18:5546-5553.
70. Leong KG, Wang BE, Johnson L, Gao WQ. 2008. Generation of a prostate from a single adult stem cell. Nature 456:804-808.
71. Leroy X, Augusto D, Leteurtre E, Gosselin B. 2002. CD30 and CD117 (c-kit) used in combination are useful for distinguishing embryonal carcinoma from seminoma. J Histochem Cytochem 50:283-285.
72. Li Q, Kondoh G, Inafuku S, Nishimune Y, Hakura A. 1996. Abrogation of c-kit/steel factor-dependent tumorigenesis by kinase defective mutants of the c-kit receptor: c-kit kinase defective mutants as candidate tools for cancer gene therapy. Cancer Res 56:4343-4346.
73. Lin AM, Rini BI, Weinberg V, Fong K, Ryan CJ, Rosenberg JE, Fong L, Small EJ. 2006. A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy. BJU Int 98:763-769.
74. Linnekin D, Mou S, Deberry CS, Weiler SR, Keller JR, Ruscetti FW, Longo DL. 1997. Stem cell factor, the JAK-STAT pathway and signal transduction. Leuk Lymphoma 27:439-444.
75. Liu K, Li L, Nisson PE, Gruber C, Jessee J, Cohen SN. 2000. Neoplastic transformation and tumorigenesis associated with sam68 protein deficiency in cultured murine fibroblasts. J Biol Chem 275:40195-40201.
76. Liu H, Chen X, Focia PJ, He X. 2007. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J 26:891-901.
77. Lizama C, Rojas-Benitez D, Antonelli M, Ludwig A, Bustamante-Marin X, Brouwer-Visser J, Moreno RD. 2010. TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis. Reproduction 140:305-317.
78. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. 1992. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70:431-442.
79. Maddens S, Charruyer A, Plo I, Dubreuil P, Berger S, Salles B, Laurent G, Jaffrezou JP. 2002. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: Implication in stem cell factor radioprotective effect. Blood 100:1294-1301.
80. Majumdar MK, Feng L, Medlock E, Toksoz D, Williams DA. 1994. Identification and mutation of primary and secondary proteolytic cleavage sites in murine stem cell factor cDNA yields biologically active, cell-associated protein. J Biol Chem 269:1237-1242.
81. Manova K, Bachvarova RF. 1991. Expression of c-kit encoded at the W locus of mice in developing embryonic germ cells and presumptive melanoblasts. Dev Biol 146:312-324.
82. Mansuroglu T, Ramadori P, Dudas J, Malik I, Hammerich K, Fuzesi L, Ramadori G. 2009. Expression of stem cell factor and its receptor c-Kit during the development of intrahepatic cholangiocarcinoma. Lab Invest 89:562-574.
83. Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, Mcniece IK, Jacobsen FW, Mendiaz EA, Birkett NC, Smith KA, Johnson MJ, Parker VP, Flores JS, Patel AC, Fisher EF, Erjavec HO, Herrera CJ, Wypych J, Sachdev RK, Pope JA, Leslie I, Wen D, Lin C, Cuppies RL, Zsebo KM. 1990. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell 63:203-211.
84. Miyazawa K, Williams DA, Gotoh A, Nishimaki J, Broxmeyer HE, Toyama K. 1995. Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form. Blood 85:641-649.
85. Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, Mcree DE. 2003. Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem 278:31461-31464.
86. Montero JC, Lopez-Perez R, San Miguel JF, Pandiella A. 2008. Expression of c-Kit isoforms in multiple myeloma: Differences in signaling and drug sensitivity. Haematologica 93:851-859.
87. Morris ID, Phillips DM, Bardin CW. 1986. Ethylene dimethanesulfonate destroys Leydig cells in the rat testis. Endocrinology 118:709-719.
88. Mruk DD, Cheng CY. 2004. Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 25:747-806.
89. Muciaccia B, Sette C, Paronetto MP, Barchi M, Pensini S, D'agostino A, Gandini L, Geremia R, Stefanini M, Rossi P. 2010. Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity. Hum Reprod 25:2188-2202.
90. Munsie M, Schlatt S, Dekretser DM, Loveland KL. 1997. Expression of stem cell factor in the postnatal rat testis. Mol Reprod Dev 47:19-25.
91. Nakai Y, Nonomura N, Oka D, Shiba M, Arai Y, Nakayama M, Inoue H, Nishimura K, Aozasa K, Mizutani Y, Miki T, Okuyama A. 2005. KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors. Biochem Biophys Res Commun 337:289-296.
92. Natali PG, Nicotra MR, Sures I, Santoro E, Bigotti A, Ullrich A. 1992. Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. Cancer Res 52:6139-6143.
93. Nocka K, Buck J, Levi E, Besmer P. 1990. Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO J 9:3287-3294.
94. Ohta H, Yomogida K, Dohmae K, Nishimune Y. 2000. Regulation of proliferation and differentiation in spermatogonial stem cells: The role of c-kit and its ligand SCF. Development 127:2125-2131.
95. Okamura A, Wakahashi K, Ishii S, Katayama Y, Yamamoto K, Matsui T. 2010. Possible alternative strategy for stage I imatinib-sensitive testicular seminoma; lessons from a case associated with Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Oncol 21:1129-1130.
96. Packer AI, Besmer P, Bachvarova RF. 1995. Kit ligand mediates survival of type A spermatogonia and dividing spermatocytes in postnatal mouse testes. Mol Reprod Dev 42:303-310.
97. Pandiella A, Bosenberg MW, Huang EJ, Besmer P, Massague J. 1992. Cleavage of membrane-anchored growth factors involves distinct protease activities regulated through common mechanisms. J Biol Chem 267:24028-24033.
98. Paronetto MP, Venables JP, Elliott DJ, Geremia R, Rossi P, Sette C. 2003. Tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCgamma1 and Sam68. Oncogene 22:8707-8715.
99. Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R, Rossi P, Sette C. 2004. Expression of a truncated form of the c-Kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am J Pathol 164:1243-1251.
100. Paulhe F, Wehrle-Haller M, Jacquier MC, Imhof BA, Tabone-Eglinger S, Wehrle-Haller B. 2009. Dimerization of Kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain. FASEB J 23:3037-3048.
101. Pauls K, Schorle H, Jeske W, Brehm R, Steger K, Wernert N, Buttner R, Zhou H. 2006. Spatial expression of germ cell markers during maturation of human fetal male gonads: An immunohistochemical study. Hum Reprod 21:397-404.
102. Pedersini R, Vattemi E, Mazzoleni G, Graiff C. 2007. Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT. Lancet Oncol 8:1039-1040.
103. Pellegrini M, Filipponi D, Gori M, Barrios F, Lolicato F, Grimaldi P, Rossi P, Jannini EA, Geremia R, Dolci S. 2008. ATRA and KL promote differentiation toward the meiotic program of male germ cells. Cell Cycle 7:3878-3888.
104. Phung B, Steingrimsson E, Ronnstrand L. 2013. Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length. Cell Signal 25:2231-2238.
105. Pytel D, Sliwinski T, Poplawski T, Ferriola D, Majsterek I. 2009. Tyrosine kinase blockers: New hope for successful cancer therapy. Anticancer Agents Med Chem 9:66-76.
106. Qiu FH, Ray P, Brown K, Barker PE, Jhanwar S, Ruddle FH, Besmer P. 1988. Primary structure of c-kit: Relationship with the CSF-1/PDGF receptor kinase family-Oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J 7:1003-1011.
107. Radford IR. 2002. Imatinib. Novartis. Curr Opin Investig Drugs 3:492-499.
108. Rajpert-De Meyts E, Skakkebaek NE. 1994. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl 17:85-92.
109. Raucci F, Di Fiore MM. 2007. The c-kit receptor protein in the testis of green frog Rana esculenta: Seasonal changes in relationship to testosterone titres and spermatogonial proliferation. Reproduction 133:51-60.
110. Reith AD, Ellis C, Lyman SD, Anderson DM, Williams DE, Bernstein A, Pawson T. 1991. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase. EMBO J 10:2451-2459.
111. Ronnstrand L. 2004. Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci 61:2535-2548.
112. Rosenberg A, Mathew P. 2013. Imatinib and prostate cancer: Lessons learned from targeting the platelet-derived growth factor receptor. Expert Opin Investig Drugs 22:787-794.
113. Roskoski R Jr. 2005. Structure and regulation of Kit protein-tyrosine kinase-The stem cell factor receptor. Biochem Biophys Res Commun 338:1307-1315.
114. Rossi P, Marziali G, Albanesi C, Charlesworth A, Geremia R, Sorrentino V. 1992. A novel c-kit transcript, potentially encoding a truncated receptor, originates within a kit gene intron in mouse spermatids. Dev Biol 152:203-207.
115. Rossi P, Lolicato F, Grimaldi P, Dolci S, Di Sauro A, Filipponi D, Geremia R. 2008. Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand. Gene Expr Patterns 8:58-70.
116. Rothschild G, Sottas CM, Kissel H, Agosti V, Manova K, Hardy MP, Besmer P. 2003. A role for kit receptor signaling in Leydig cell steroidogenesis. Biol Reprod 69:925-932.
117. Sa R, Miranda C, Carvalho F, Barros A, Sousa M. 2013. Expression of stem cell markers: OCT4, KIT, ITGA6, and ITGB1 in the male germinal epithelium. Syst Biol Reprod Med 59:233-243.
118. Sakuma Y, Sakurai S, Oguni S, Hironaka M, Saito K. 2003. Alterations of the c-kit gene in testicular germ cell tumors. Cancer Sci 94:486-491.
119. Sakuma Y, Matsukuma S, Yoshihara M, Sakurai S, Nishii M, Kishida T, Kubota Y, Nagashima Y, Inayama Y, Sasaki T, Nakamura Y, Miura T, Kameda Y, Tsuchiya E, Miyagi Y. 2008. Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan. Cancer Lett 259:119-126.
120. Sandlow JI, Feng HL, Cohen MB, Sandra A. 1996. Expression of c-KIT and its ligand, stem cell factor, in normal and subfertile human testicular tissue. J Androl 17:403-408.
121. Sandlow JI, Feng HL, Sandra A. 1997. Localization and expression of the c-kit receptor protein in human and rodent testis and sperm. Urology 49:494-500.
122. Sandlow JI, Feng HL, Zheng LJ, Sandra A. 1999. Migration and ultrastructural localization of the c-kit receptor protein in spermatogenic cells and spermatozoa of the mouse. J Urol 161:1676-1680.
123. Sato T, Yokonishi T, Komeya M, Katagiri K, Kubota Y, Matoba S, Ogonuki N, Ogura A, Yoshida S, Ogawa T. 2012. Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice. Proc Natl Acad Sci USA 109:16934-16938.
124. Schnabel D, Ramirez L, Gertsenstein M, Nagy A, Lomeli H. 2005. Ectopic expression of KitD814Y in spermatids of transgenic mice, interferes with sperm morphogenesis. Dev Dyn 233:29-40.
125. Schrans-Stassen BH, Van De Kant HJ, De Rooij DG, Van Pelt AM. 1999. Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia. Endocrinology 140:5894-5900.
126. Sette C, Bevilacqua A, Geremia R, Rossi P. 1998. Involvement of phospholipase Cgamma1 in mouse egg activation induced by a truncated form of the C-kit tyrosine kinase present in spermatozoa. J Cell Biol 142:1063-1074.
127. Sette C, Paronetto MP, Barchi M, Bevilacqua A, Geremia R, Rossi P. 2002. Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. EMBO J 21:5386-5395.
128. Shafik A, Shafik I, El-Sibai O. 2005. Identification of c-kit-positive cells in the human prostate: The interstitial cells of Cajal. Arch Androl 51:345-351.
129. Shima Y, Miyabayashi K, Haraguchi S, Arakawa T, Otake H, Baba T, Matsuzaki S, Shishido Y, Akiyama H, Tachibana T, Tsutsui K, Morohashi K. 2013. Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes. Mol Endocrinol 27:63-73.
130. Sikarwar AP, Reddy KV. 2008. siRNA-mediated silencing of c-kit in mouse primary spermatogonial cells induces cell cycle arrest. Oligonucleotides 18:145-160.
131. Sikarwar AP, Rambabu MK, Reddy KV. 2008. Differential regulation of gene expression in mouse spermatogonial cells after blocking c-kit-SCF interaction with RNAi. J RNAi Gene Silencing 4:302-311.
132. Simak R, Capodieci P, Cohen DW, Fair WR, Scher H, Melamed J, Drobnjak M, Heston WD, Stix U, Steiner G, Cordon-Cardo C. 2000. Expression of c-kit and kit-ligand in benign and malignant prostatic tissues. Histol Histopathol 15:365-374.
133. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. 2005. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615-625.
134. Slack JK, Adams RB, Rovin JD, Bissonette EA, Stoker CE, Parsons JT. 2001. Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene 20:1152-1163.
135. Sorrentino V, Giorgi M, Geremia R, Besmer P, Rossi P. 1991. Expression of the c-kit proto-oncogene in the murine male germ cells. Oncogene 6:149-151.
136. Strohmeyer T, Peter S, Hartmann M, Munemitsu S, Ackermann R, Ullrich A, Slamon DJ. 1991. Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors. Cancer Res 51:1811-1816.
137. Strohmeyer T, Reese D, Press M, Ackermann R, Hartmann M, Slamon D. 1995. Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue. J Urol 153:511-515.
138. Tajima Y, Onoue H, Kitamura Y, Nishimune Y. 1991. Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in SId mutant mice. Development 113:1031-1035.
139. Takaoka A, Toyota M, Hinoda Y, Itoh F, Mita H, Kakiuchi H, Adachi M, Imai K. 1997. Expression and identification of aberrant c-kit transcripts in human cancer cells. Cancer Lett 115:257-261.
140. Tate G, Suzuki T, Kishimoto K, Mitsuya T. 2005. A c-KIT codon 816 mutation, D816H, in the testicular germ cell tumor: Case report of a Japanese patient with bilateral testicular seminomas. Acta Med Okayama 59:33-36.
141. Teerds KJ, De Boer-Brouwer M, Dorrington JH, Balvers M, Ivell R. 1999. Identification of markers for precursor and leydig cell differentiation in the adult rat testis following ethane dimethyl sulphonate administration. Biol Reprod 60:1437-1445.
142. Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA. 1999. Activating c-kit gene mutations in human germ cell tumors. Am J Pathol 154:1643-1647.
143. Toyota M, Hinoda Y, Itoh F, Takaoka A, Imai K, Yachi A. 1994. Complementary DNA cloning and characterization of truncated form of c-kit in human colon carcinoma cells. Cancer Res 54:272-275.
144. Tsikolia N, Merkwitz C, Sass K, Sakurai M, Spanel-Borowski K, Ricken AM. 2009. Characterization of bovine fetal Leydig cells by KIT expression. Histochem Cell Biol 132:623-632.
145. Tsuura Y, Hiraki H, Watanabe K, Igarashi S, Shimamura K, Fukuda T, Suzuki T, Seito T. 1994. Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: Immunohistochemical study on formalin-fixed, paraffin-embedded tissues. Virchows Arch 424:135-141.
146. Tu J, Fan L, Tao K, Zhu W, Li J, Lu G. 2007. Stem cell factor affects fate determination of human gonocytes in vitro. Reproduction 134:757-765.
147. Turner AM, Bennett LG, Lin NL, Wypych J, Bartley TD, Hunt RW, Atkins HL, Langley KE, Parker V, Martin F, Virgina CB. 1995. Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines. Blood 85:2052-2058.
148. Ullrich A, Schlessinger J. 1990. Signal transduction by receptors with tyrosine kinase activity. Cell 61:203-212.
149. Unni SK, Modi DN, Pathak SG, Dhabalia JV, Bhartiya D. 2009. Stage-specific localization and expression of c-kit in the adult human testis. J Histochem Cytochem 57:861-869.
150. Van Der Aa F, Roskams T, Blyweert W, De Ridder D. 2003. Interstitial cells in the human prostate: A new therapeutic target? Prostate 56:250-255.
151. Vigodner M, Lewin LM, Shochat L, Golan R. 2001. Spermatogenesis in the golden hamster: The role of c-kit. Mol Reprod Dev 60:562-568.
152. Vincent S, Segretain D, Nishikawa S, Nishikawa SI, Sage J, Cuzin F, Rassoulzadegan M. 1998. Stage-specific expression of the Kit receptor and its ligand (KL) during male gametogenesis in the mouse: A Kit-KL interaction critical for meiosis. Development 125:4585-4593.
153. Wang Y, Suominen JS, Hakovirta H, Parvinen M, Martinand-Mari C, Toppari J, Robbins I. 2004. Survivin expression in rat testis is upregulated by stem-cell factor. Mol Cell Endocrinol 218:165-174.
154. Wartenberg H. 1976. Comparative cytomorphologic aspects of the male germ cells, especially of the "Gonia". Andrologia 8:117-130.
155. Wiesner C, Nabha SM, Dos Santos EB, Yamamoto H, Meng H, Melchior SW, Bittinger F, Thuroff JW, Vessella RL, Cher ML, Bonfil RD. 2008. C-kit and its ligand stem cell factor: Potential contribution to prostate cancer bone metastasis. Neoplasia 10:996-1003.
156. Williams DE, Eisenman J, Baird A, Rauch C, Van Ness K, March CJ, Park LS, Martin U, Mochizuki DY, Boswell HS, Burgess GS, Cosma D, Stewart DL. 1990. Identification of a ligand for the c-kit proto-oncogene. Cell 63:167-174.
157. Willmore-Payne C, Holden JA, Chadwick BE, Layfield LJ. 2006. Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis. Mod Pathol 19:1164-1169.
158. Wypych J, Bennett LG, Schwartz MG, Clogston CL, Lu HS, Broudy VC, Bartley TD, Parker VP, Langley KE. 1995. Soluble kit receptor in human serum. Blood 85:66-73.
159. Yan W, Kero J, Huhtaniemi I, Toppari J. 2000a. Stem cell factor functions as a survival factor for mature Leydig cells and a growth factor for precursor Leydig cells after ethylene dimethane sulfonate treatment: Implication of a role of the stem cell factor/c-Kit system in Leydig cell development. Dev Biol 227:169-182.
160. Yan W, Samson M, Jegou B, Toppari J. 2000b. Bcl-w forms complexes with Bax and Bak, and elevated ratios of Bax/Bcl-w and Bak/Bcl-w correspond to spermatogonial and spermatocyte apoptosis in the testis. Mol Endocrinol 14:682-699.
161. Yan W, Suominen J, Toppari J. 2000c. Stem cell factor protects germ cells from apoptosis in vitro. J Cell Sci 113:161-168.
162. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A. 1987. Human proto-oncogene c-kit: A new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J 6:3341-3351.
163. Yoshinaga K, Nishikawa S, Ogawa M, Hayashi S, Kunisada T, Fujimoto T. 1991. Role of c-kit in mouse spermatogenesis: Identification of spermatogonia as a specific site of c-kit expression and function. Development 113:689-699.
164. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. 2007. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell 130:323-334.
165. Zhang Z, Zhang R, Joachimiak A, Schlessinger J, Kong XP. 2000. Crystal structure of human stem cell factor: Implication for stem cell factor receptor dimerization and activation. Proc Natl Acad Sci USA 97:7732-7737.
166. Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hsu RY, Birkett NC, Okino KH, Murdock DC, Jacobsen FW, Langley KE, Smith KA, Takeish T, Cattanach BM, Galli SJ, Suggs SV. 1990. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63:213-224.