Hedgehog-Gli signaling in brain tumors: Stem cells and paradevelopmental programs in cancer

Cancer Letters

Volumn 204, Issue 2, 2004, Pages 145-157

  Ruiz I Altaba, Ariel ^a   Stecca, Barbara ^a   Sánchez, Pilar ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Brain; Cancer; Cerebellum; Cortex; Cyclopamine; Embryo; Frog; Gli1; Gli2; Gli3; Glioma; Hedgehog; Human; Inhibitors; Medulloblastoma; Model system; Mouse; Patched; Progenitor; Small molecule; Smoothened; Sonic hedgehog; Stem cell; Targets; Therapeutic agents; Tumor

Indexed keywords

SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI1;

BRAIN GROWTH; BRAIN TUMOR; CANCER; CANCER INHIBITION; CARCINOGENESIS; CELL PROLIFERATION; DISEASE COURSE; GENETIC REGULATION; GERMINATION; HEDGEHOG; HUMAN; MEDULLOBLASTOMA; NONHUMAN; PRECURSOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; TUMOR CELL;

ANURA; ERINACEIDAE; VERTEBRATA;

EID: 0842265834     PISSN: 03043835     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0304-3835(03)00451-8     Document Type: Article

References (155)

1. Kleihues P., Cavenee W.K. Pathology and Genetics of Tumors of the Nervous System. 1997;International Agency for Research on Cancer (IARC) World Health Organization, Lyon, France.
2. Ackerman A.B. Neoplasms with Follicular Differentiation. 2001;Ardor Scrsibendi Publishers, New York.
3. Perou C.M., Sorlie T., Eisen M.B., van de Rijn M., Jeffrey S.S., Rees C.A., Pollack J.R., Ross D.T., Johnsen H., Akslen L.A., Fluge O., Pergamenschikov A., Williams C., Zhu S.X., Lonning P.E., Borresen-Dale A.L., Brown P.O., Botstein D. Molecular portraits of human breast tumors. Nature. 406:2000;747-752.
4. Sallinen S.L., Sallinen P.K., Haapasalo H.K., Helin H.J., Helen P.T., Schraml P., Kallioniemi O.P., Kononen J. Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res. 60:2000;6617-6622.
5. MacDonald T.J., Brown K.M., LaFleur B., Peterson K., Lawlor C., Chen Y., Packer R.J., Cogen P., Stephan D.A. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet. 29:2001;143-152.
6. Gutmann D.H., Huang Z.Y., Hedrick N.M., Ding H., Guha A., Watson M.A. Mouse glioma gene expression profiling identifies novel human glioma-associated genes. Ann. Neurol. 51:2002;393-405.
7. Pomeroy S.L., Tamayo P., Gaasenbeek M., Sturla L.M., Angelo M., McLaughlin M.E., Kim J.Y., Goumnerova L.C., Black P.M., Lau C., Allen J.C., Zagzag D., Olson J.M., Curran T., Wetmore C., Biegel J.A., Poggio T., Mukherjee S., Rifkin R., Califano A., Stolovitzky G., Louis D.N., Mesirov J.P., Lander E.S., Golub T.R. Prediction of central nervous system embryonal tumor outcome based on gene expression. Nature. 415:2002;436-442.
8. Maher E.A., Furnari F.B., Bachoo R.M., Rowitch D.H., Louis D.N., Cavenee W.K., DePinho R.A. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 15:2001;1311-1333.
9. Holland E.C. Gliomagenesis: genetic alterations and mouse models. Nat. Rev. Genet. 2:2001;120-129.
10. Ding H., Roncari L., Shannon P., Wu X., Lau N., Karaskova J., Gutmann D.H., Squire J.A., Nagy A., Guha A. Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res. 61:2001;3826-3836.
11. Holland E.C., Celestino J., Dai C., Schaefer L., Sawaya R.E., Fuller G.N. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat. Genet. 25:2000;55-57.
12. Uhrbom L., Dai C., Celestino J.C., Rosenblum M.K., Fuller G.N., Holland E.C. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res. 62:2002;5551-5558.
13. Nishikawa R., Ji X.D., Harmon R.C., Lazar C.S., Gill G.N., Cavenee W.K., Huang H.J. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl. Acad. Sci. USA. 91:1994;7727-7731.
14. Holland E.C., Hively W.P., DePinho R.A., Varmus H.E. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev. 12:1998;3675-3685.
15. Bachoo R.M., Maher E.A., Ligon K.L., Sharpless N.E., Chan S.S., You M.J., Tang Y., DeFrances J., Stover E., Weissleder R., Rowitch D.H., Louis D.N., DePinho R.A. Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell. 1:2002;269-277.
16. Reilly K.M., Loisel D.A., Bronson R.T., McLaughlin M.E., Jacks T. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat. Genet. 26:2000;109-113.
17. Dai C., Celestino J.C., Okada Y., Louis D.N., Fuller G.N., Holland E.C. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 15:2001;1913-1925.
18. Marino S., Vooijs M., van Der Gulden H., Jonkers J., Berns A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14:2000;994-1004.
19. Lee Y., McKinnon P.J. DNA Ligase IV suppresses medulloblastoma growth. Cancer Res. 62:2002;6395-6399.
20. Tong W.-M., Ohgaki H., Huang H., Granier C., Kleihues P., Wang Z.-Q. Null mutation of DNA strand break-binding molecule poly (ADP-ribose) polymerase causes medulloblastomas in p53-/- mice. Am. J. Pathol. 162:2003;343-352.
21. Goodrich L.V., Milenkovic L., Higgins K.M., Scott M.P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 277:1997;1109-1113.
22. Wetmore C., Eberhart D.E., Curran T. Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res. 61:2001;513-516.
23. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 10:2000;57-70.
24. Polakis P. Wnt signaling and cancer. Genes Dev. 14:2000;1837-1851.
25. Meuwissen R., Jonkers J., Berns A. Mouse models for sporadic cancer. Exp. Cell Res. 264:2001;100-110.
26. Wu X., Pandolfi P.P. Mouse models for multistep tumorigenesis. Trends Cell Biol. 11:2001;S2-S9.
27. Corcoran R.B., Scott M.P. A mouse model for medulloblastoma and basal cell nevus syndrome. J. Neurooncol. 53:2001;307-318.
28. Zhu Y., Parada L.F. The molecular and genetic basis of neurological tumors. Nat. Rev. Cancer. 2:2002;616-626.
29. Ruiz i Altaba A., Sanchez P., Dahmane N. The hedgehog-Gli pathway in cancer. Nature Review Cancer. 2:2002;361-372.
30. Knudson A.G. Jr. Chasing the cancer demon. Annu. Rev. Genet. 34:2000;1-19.
31. Felsher D.W., Bishop J.M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell. 4:1999;199-207.
32. Pelengaris S., Littlewood T., Khan M., Elia G., Evan G. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol. Cell. 3:1999;565-577.
33. Chin L., Tam A., Pomerantz J., Wong M., Holash J., Bardeesy N., Shen Q., O'Hagan R., Pantginis J., Zhou H., Horner J.W. II, Cordon-Cardo C., Yancopoulos G.D., DePinho R.A. Essential role for oncogenic Ras in tumor maintenance. Nature. 400:1999;468-472.
34. Huettner C.S., Zhang P., Van Etten R.A., Tenen D.G. Reversibility of acute B-cell leukemia induced by BCR-ABL1. Nat. Genet. 24:2000;57-60.
35. Fisher G.H., Wellen S.L., Klimstra D., Lenczowski J.M., Tichelaar J.W., Lizak M.J., Whitsett J.A., Koretsky A., Varmus H.E. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev. 15:2001;3249-3262.
36. Jackson E.L., Willis N., Mercer K., Bronson R.T., Crowley D., Montoya R., Jacks T., Tuveson D.A. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15:2001;3243-3248.
37. Gorre M.E., Mohammed M., Ellwood K., Hsu N., Paquette R., Rao P.N., Sawyers C.L. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 293:2001;876-880.
38. Gunther E., Moody S.E., Belka G.K., Hahn K.T., Innocent N., Dugan K.D., Cardiff R.C., Chodosh L.A. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev. 17:2003;488-501.
39. Soussi T., Beroud C. Assessing TP53 status in human tumors to evaluate clinical outcome. Nat. Rev. Cancer. 1:2001;233-240.
40. Melino G., De Laurenzi V., Vousden K.H. p73: Friend or foe in tumorigenesis. Nat. Rev. Cancer. 2:2002;605-615.
41. Yang A., Kaghad M., Caput D., McKeon F. On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet. 18:2002;90-95.
42. Evan G.I. Proliferation, cell cycle and apoptosis in cancer. Nature. 411:2001;342-348.
43. Sell S., Pierce G.B. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinoma and epithelial cancers. Lab. Invest. 70:1994;6-22.
44. Reya T., Morrison S.J., Clarke M.F., Weissman I.L. Stem cells, cancer, and cancer stem cells. Nature. 414:2001;105-111.
45. Lapidot T., Sirard C., Vormoor J., Murdoch B., Hoang T., Caceres-Cortex J., Minden M., Paterson B., Caligiuri M.A., Dick J.E. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 367:1994;645-648.
46. Bonnet D., Dick J.E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3:1997;730-737.
47. Larochelle A., Vormoor J., Hanenberg H., Wang J.C.Y., Bhatia M., Moritz T., Murdoch B., Xiao X.L., Kato I., Williams D.A., Dick J.E. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implication for gene therapy. Nat. Med. 2:1996;1329-1337.
48. Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA. 100:2003;3983-3988.
49. Nusslein-Volhard C., Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 287:1980;795-801.
50. Lee J.J., von Kessler D.P., Parks S., Beachy P.A. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 71:1992;33-50.
51. Mohler J., Vani K. Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila. Development. 115:1992;957-971.
52. Tabata T., Eaton S., Kornberg T.B. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev. 6:1992;2635-2645.
53. Ingham P.W., McMahon A.P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15:2001;3059-3087.
54. Mullor J.L., Sánchez P., Ruiz i Altaba A. Pathways and consequences: hedgehog signaling in human disease. Trends Cell Biol. 12:2002;562-569.
55. Riddle R.D., Johnson R.L., Laufer E., Tabin C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell. 75:1993;1401-1416.
56. Krauss S., Concordet J.P., Ingham P.W. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell. 75:1993;1431-1444.
57. Echelard Y., Epstein D.J., St-Jacques B., Shen L., Mohler J., McMahon J.A., McMahon A.P. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 75:1993;1417-1430.
58. Roelink H., Augsburger A., Heemskerk J., Korzh V., Norlin S., Ruiz i Altaba A., Tanabe Y., Placzek M., Edlund T., Jessell T.M. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Cell. 76:1994;761-775.
59. Jessell T.M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1:2000;20-29.
60. Ruiz i Altaba A., Palma V., Dahmane N. Hedgehog-Gli signalling and the growth of the brain. Nat. Rev. Neuro. 3:2002;24-33.
61. Ruiz i Altaba A. The works of GLI and the power of hedgehog. Nat. Cell Biol. 1:1999;147-148.
62. Ho K.S., Scott M.P. Sonic hedgehog in the nervous system: functions, modifications and mechanisms. Curr. Opin. Neurobiol. 12:2002;57-63.
63. Nybakken K., Perrimon N. Hedgehog signal transduction: recent findings. Curr. Opin. Genet. Dev. 12:2002;503-511.
64. Sasaki H., Nishizaki Y., Hui C., Nakafuku M., Kondoh H. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development. 126:1999;3915-3924.
65. Bai C.B., Auerbach W., Lee J.S., Stephen D., Joyner A.L. Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 129:2002;4753-4761.
66. Kinzler K.W., Bigner S.H., Bigner D.D., Trent J.M., Law M.L., O'Brien S.J., Wong A.J., Vogelstein B. Identification of an amplified, highly expressed gene in a human glioma. Science. 236:1987;70-73.
67. Louro I.D., Bailey E.C., Li X., South L.S., McKie-Bell P.R., Yoder B.K., Huang C.C., Johnson M.R., Hill A.E., Johnson R.L., Ruppert J.M. Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation. Cancer Res. 62:2002;5867-5873.
68. Ruppert J.M., Vogelstein B., Kinzler K.W. The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol. Cell Biol. 11:1991;1724-1728.
69. Salgaller M., Pearl D., Stephens R. In situ hybridization with single-stranded RNA probes to demonstrate infrequently elevated gli mRNA and no increased ras mRNA levels in meningiomas and astrocytomas. Cancer Lett. 57:1991;243-253.
70. Xiao H., Goldthwait D.A., Mapstone T. A search for gli expression in tumors of the central nervous system. Pediatr. Neurosurg. 20:1994;178-182.
71. Dahmane N., Lee J., Robins P., Heller P., Ruiz i Altaba A. Activation of Gli1 and the Sonic hedgehog signaling pathway in skin tumors. Nature. 389:1997;876-881.
72. Dahmane N., Sanchez P., Gitton Y., Palma V., Sun T., Beyna M., Weiner H., Ruiz i Altaba A. The SHH-Gli pathway in brain growth and tumorigenesis. Development. 128:2001;5201-5212.
73. Nilsson M., Unden A.B., Krause D., Malmqwist U., Raza K., Zaphiropoulos P.G., Toftgard R. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc. Natl. Acad. Sci. USA. 97:2000;3438-3443.
74. Johnson R.L., Rothman A.L., Xie J., Goodrich L.V., Bare J.W., Bonifas J.M., Quinn A.G., Myers R.M., Cox D.R., Epstein E.H. Jr., Scott M.P. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 272:1996;1668-1671.
75. Hahn H., Wicking C., Zaphiropoulous P.G., Gailani M.R., Shanley S., Chidambaram A., Vorechovsky I., Holmberg E., Unden A.B., Gillies S., Negus K., Smyth I., Pressman C., Leffell D.J., Gerrard B., Goldstein A.M., Dean M., Toftgard R., Chenevix-Trench G., Wainwright B., Bale A.E. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 85:1996;841-851.
76. Berman D.M., Karhadkar S.S., Hallahan A.R., Pritchard J.I., Eberhart C.G., Watkins D.N., Chen J.K., Cooper M.K., Taipale J., Olson J.M., Beachy P.A. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 297:2002;1559-1561.
77. Weiner H.L., Bakst R., Hurlbert M.S., Ruggiero J., Ahn E., Lee W.S., Stephen D., Zagzag D., Joyner A.L., Turnbull D.H. Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1. Cancer Res. 62:2002;6385-6389.
78. Dahmane N., Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 126:1999;3089-3100.
79. Wallace V.A. Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr. Biol. 9:1999;445-448.
80. Wechsler-Reya R.J., Scott M.P. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron. 22:1999;103-114.
81. Lai K., Kaspar B.K., Gage F.H., Schaffer D.V. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat. Neurosci. 6:2003;21-27.
82. V. Palma, D. Lim, N. Dahmane, P. Sanchez, Y. Gitton, A. Alvarez-Buylla, A. Ruiz i Altaba, 2003, Submitted for publication.
83. Hahn H., Wojnowski L., Zimmer A.M., Hall J., Miller G., Zimmer A. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat. Med. 4:1998;619-622.
84. Gailani M.R., Stahle-Backdahl M., Leffell D.J., Glynn M., Zaphiropoulos P.G., Pressman C., Unden A.B., Dean M., Brash D.E., Bale A.E., Toftgard R. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat. Genet. 14:1996;78-81.
85. Fan H., Oro A.E., Scott M.P., Khavari P.A. Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog. Nat. Med. 3:1997;788-792.
86. Oro A.E., Higgins K.M., Hu Z., Bonifas J.M., Epstein E.H. Jr., Scott M.P. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science. 276:1997;817-821.
87. Xie J., Murone M., Luoh S.M., Ryan A., Gu Q., Zhang C., Bonifas J.M., Lam C.W., Hynes M., Goddard A., Rosenthal A., Epstein E.H. Jr., de Sauvage F.J. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 391:1998;90-92.
88. Aszterbaum M., Epstein J., Oro A., Douglas V., LeBoit P.E., Scott M.P., Epstein E.H. Jr. Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice. Nat. Med. 5:1999;1285-1291.
89. Grachtchouk M., Mo R., Yu S., Zhang X., Sasaki H., Hui C.C., Dlugosz A.A. Basal cell carcinomas in mice overexpressing Gli2 in skin. Nat. Genet. 24:2000;216-217.
90. Sheng H., Goich S., Wang A., Grachtchouk M., Lowe L., Mo R., Lin K., de Sauvage F.J., Sasaki H., Hui C.C., Dlugosz A.A. Dissecting the oncogenic potential of Gli2: deletion of an NH(2)-terminal fragment alters skin tumor phenotype. Cancer Res. 62:2002;5308-5316.
91. Williams J.A., Guicherit O.M., Zaharian B.I., Xu Y., Chai L., Wichterie H., Kon C., Gatchalian C., Porter J.A., Rubin L.L., Wang F.Y. Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Proc. Natl. Acad. Sci. USA. 100:2003;4616-4621.
92. Oro A.E., Scott M.P. Splitting hairs: dissecting roles of signaling systems in epidermal development. Cell. 95:1998;575-578.
93. Wicking C., Smyth I., Bale A. The hedgehog signaling pathway in tumorigenesis and development. Oncogene. 18:1999;7844-7851.
94. Watkins D.N., Berman D.M., Burkholder S.G., Wang B., Beachy P.A., Baylin S.B. Hedgehog signaling within airway epithelial progenitors and in small-cell lung cancer. Nature. 422:2003;313-317.
95. Lee J., Platt K., Censullo P., Ruiz i Altaba A. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development. 124:1997;2537-2552.
96. Hynes M., Stone D.M., Dowd M., Pitts-Meek S., Goddard A., Gurney A., Rosenthal A. Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron. 19:1997;15-26.
97. Ghali L., Wong S.T., Green J., Tidman N., Quinn A.G. Gli1 protein is expressed in basal cell carcinomas, outer root sheath keratinocytes and a subpopulation of mesenchymal cells in normal human skin. J. Invest. Dermatol. 113:1999;595-599.
98. Stein U., Eder C., Karsten U., Haensch W., Walther W., Schlag P.M. GLI gene expression in bone and soft tissue sarcomas of adult patients correlates with tumor grade. Cancer Res. 59:1999;1890-1895.
99. Bonifas J.M., Pennypacker S., Chuang P.T., McMahon A.P., Williams M., Rosenthal A., De Sauvage F.J., Epstein E.H. Jr. Activation of expression of hedgehog target genes in basal cell carcinomas. J. Invest. Dermatol. 116:2001;739-742.
100. Regl G., Neill G.W., Eichberger T., Kasper M., Ikram M.S., Koller J., Hintner H., Quinn A.G., Frischauf A.M., Aberger F. Human GLI1 and GLI2 are part of a positive feedback mechanism in basal cell carcinoma. Oncogene. 21:2002;5529-5539.
101. Globus J.H., Kuhlenbeck H. The subependymal cell plate (matrix) and its relationship to brain tumors of the ependymal type. J. Neuropathol. Exp. Neurol. 3:1944;1-35.
102. Incardona J.P., Gaffield W., Kapur R.P., Roelink H. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development. 125:1998;3553-3562.
103. Cooper M.K., Porter J.A., Young K.E., Beachy P.A. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science. 280:1998;1603-1607.
104. Taipale J., Chen J.K., Cooper M.K., Wang B., Mann R.K., Milenkovic L., Scott M.P., Beachy P.A. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature. 406:2000;1005-1009.
105. Pazzaglia S., Mancuso M., Atkinson M.J., Tanori M., Rebessi S., Majo V.D., Covelli V., Hahn H., Saran A. High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice. Oncogene. 21:2002;7580-7584.
106. Raffel C., Jenkins R.B., Frederick L., Hebrink D., Alderete B., Fults D.W., James C.D. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57:1997;842-845.
107. Wolter M., Reifenberger J., Sommer C., Ruzicka T., Reifenberger G. Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 57:1997;2581-2585.
108. Pietsch T., Waha A., Koch A., Kraus J., Albrecht S., Tonn J., Sorensen N., Berthold F., Henk B., Schmandt N., Wolf H.K., von Deimling A., Wainwright B., Chenevix-Trench G., Wiestler O.D., Wicking C. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res. 57:1997;2085-2088.
109. Reifenberger J., Wolter M., Weber R.G., Megahed M., Ruzicka T., Lichter P., Reifenberger G. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 58:1998;1798-1803.
110. Dong J., Gailani M.R., Pomeroy S.L., Reardon D., Bale A.E. Identification of PATCHED mutations in medulloblastomas by direct sequencing. Hum. Mutat. 16:2000;89-90.
111. Zurawel R.H., Allen C., Chiappa S., Cato W., Biegel J., Cogen P., de Sauvage F., Raffel C. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer. 27:2000;44-51.
112. Taylor M.D., Liu L., Raffel C., Hui C.C., Mainprize T.G., Zhang X., Agatep R., Chiappa S., Gao L., Lowrance A., Hao A., Goldstein A.M., Stavrou T., Scherer S.W., Dura W.T., Wainwright B., Squire J.A., Rutka J.T., Hogg D. Mutations in SUFU predispose to medulloblastoma. Nat. Genet. 31:2002;306-310.
113. Zurawel R.H., Allen C., Wechsler-Reya R., Scott M.P., Raffel C. Evidence that haploinsufficiency of Ptch leads to medulloblastoma in mice. Genes Chromosomes Cancer. 28:2000;77-81.
114. Wetmore C., Eberhart D.E., Curran T. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Cancer Res. 60:2000;2239-2246.
115. Smyth I., Narang M.A., Evans T., Heimann C., Nakamura Y., Chenevix-Trench G., Pietsch T., Wicking C., Wainwright B.J. Isolation and characterization of human patched 2 (PTCH2), a putative tumor suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. Hum. Mol. Genet. 8:1999;291-297.
116. Zaphiropoulos P.G., Unden A.B., Rahnama F., Hollingsworth R.E., Toftgard R. PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas. Cancer Res. 59:1999;787-792.
117. Katayama M., Yoshida K., Ishimori H., Katayama M., Kawase T., Motoyama J., Kamiguchi H. Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy. J. Neurooncol. 59:2002;107-115.
118. Goodrich L.V., Johnson R.L., Milenkovic L., McMahon J.A., Scott M.P. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev. 10:1996;301-312.
119. Unden A.B., Zaphiropoulos P.G., Bruce K., Toftgard R., Stahle-Backdahl M. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma. Cancer Res. 57:1997;2336-2340.
120. Park H.L., Bai C., Platt K.A., Matise M.P., Beeghly A., Hui C.C., Nakashima M., Joyner A.L. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development. 127:2000;1593-1605.
121. Erez A., Ilan T., Amariglio N., Muler I., Brok-Simoni F., Rechavi G., Izraeli S. GLI3 is not mutated commonly in sporadic medulloblastomas. Cancer. 95:2002;28-31.
122. Darnell J.E. Jr. Transcription factors as targets for cancer therapy. Nat. Rev. Cancer. 2:2002;740-749.
123. Brash D.E., Ponten J. Skin precancer. Cancer Surv. 32:1998;69-113.
124. Zhang H., Ping X.L., Lee P.K., Wu X.L., Yao Y.J., Zhang M.J., Silvers D.N., Ratner D., Malhotra R., Peacocke M., Tsou H.C. Role of PTCH and p53 genes in early-onset basal cell carcinoma. Am. J. Pathol. 158:2001;381-385.
125. Ling G., Ahmadian A., Persson A., Unden A.B., Afink G., Williams C., Uhlen M., Toftgard R., Lundeberg J., Ponten F. PATCHED and p53 gene alterations in sporadic and hereditary basal cell cancer. Oncogene. 20:2001;7770-7778.
126. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1997;1943-1947.
127. Steck P.A., Pershouse M.A., Jasser S.A., Yung W.K., Lin H., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng D.H., Tavtigian S.V. Identification of a candidate tumor suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15:1997;356-362.
128. Wang S.I., Puc J., Li J., Bruce J.N., Cairns P., Sidransky D., Parsons R. Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 57:1997;4183-4186.
129. Zhou X.P., Li Y.J., Hoang-Xuan K., Laurent-Puig P., Mokhtari K., Longy M., Sanson M., Delattre J.Y., Thomas G., Hamelin R. Mutational analysis of the PTEN gene in gliomas: molecular and pathological correlations. Int. J. Cancer. 84:1999;150-154.
130. Schwab M., Alitalo K., Klempnauer K.H., Varmus H.E., Bishop J.M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature. 305:1983;245-248.
131. Kohl N.E., Kanda N., Schreck R.R., Bruns G., Latt S.A., Gilbert F., Alt F.W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 35:1983;359-367.
132. Lee W.H., Murphree A.L., Benedict W.F. Expression and amplification of the N-myc gene in primary retinoblastoma. Nature. 309:1984;458-460.
133. Groszer M., Erickson R., Scripture-Adams D.D., Lesche R., Trumpp A., Zack J.A., Kornblum H.I., Liu X., Wu H. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science. 294:2001;2186-2189.
134. Knoepfler P.S., Cheng P.F., Eisenman R.N. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev. 16:2002;2699-2712.
135. Fults D., Pedone C., Dai C., Holland E.C. MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo. Neoplasia. 4:2002;32-39.
136. Kenney A.M., Cole M.D., Rowitch D.H. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development. 130:2003;15-28.
137. Bigner S.H., Friedman H.S., Vogelstein B., Oakes W.J., Bigner D.D. Amplification of the c-Myc gene in human medulloblastoma cell lines and xenografts. Cancer Res. 50:1990;2347-2350.
138. Bruggers,K C.S., Tai F., Murdock T., Sivak L., Le K., Perkins S.L., Coffin C.M., Carroll W.L. Expression of the c-Myc protein in childhood medulloblastoma. J. Pediatr. Hematol. Oncol. 20:1998;18-25.
139. Nicholas M., Wolfer A., Raj K., Kummer J.A., Mill P., van Noort M., Hui C.-., Clevers H., Dotto G.P., Radtke F. Notch1 functions as a tumor suppressor in mouse skin. Nat. Genet. 33:2003;416-421.
140. Kenney A.M., Rowitch D.H. Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol. Cell Biol. 20:2000;9055-9067.
141. Teh M.T., Wong S.T., Neill G.W., Ghali L.R., Philpott M.P., Quinn A.G. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 62:2002;4773-4780.
142. Mullor J.L., Dahmane N., Sun T., Ruiz i Altaba A. Wnt signals are targets and mediators of Gli function. Curr. Biol. 11:2001;769-773.
143. Hahn H., Wojnowski L., Specht K., Kappler R., Calzada-Wack J., Potter D., Zimmer A., Muller U., Samson E., Quintanilla-Martinez L. Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J. Biol. Chem. 275:2000;28341-28344.
144. St-Jacques B., Dassule H.R., Karavanova I., Botchkarev V.A., Li J., Danielian P.S., McMahon J.A., Lewis P.M., Paus R., McMahon A.P. Sonic hedgehog signaling is essential for hair development. Curr. Biol. 8:1998;1058-1068.
145. van den Brink G.R., Hardwick J.C., Tytgat G.N., Brink M.A., Ten Kate F.J., Van Deventer S.J., Peppelenbosch M.P. Sonic hedgehog regulates gastric gland morphogenesis in man and mouse. Gastroenterology. 121:2001;317-328.
146. Keeler R.F. Teratogenic compounds of Veratrum californicum (Durand) X. Cyclopia in rabbits produced by cyclopamine. Teratology. 3:1970;175-180.
147. Keeler R.F., Baker D.C. Oral, osmotic minipump, and intramuscular administration to sheep of the Veratrum alkaloid cyclopamine. Proc. Soc. Exp. Biol. Med. 192:1989;153-156.
148. Bhardwaj G., Murdoch B., Wu D., Baker D.P., Williams K.P., Chadwick K., Ling L.E., Karanu F.N., Bhatia M. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat. Immunol. 2:2001;172-180.
149. Robbins D.J., Nybakken K.E., Kobayashi R., Sisson J.C., Bishop J.M., Therond P.P. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell. 90:1997;225-234.
150. Kalderon D. Similarities between the Hedgehog and Wnt signaling pathways. Trends Cell Biol. 12:2002;523-531.
151. Brewster R., Mullor J.L., Ruiz i Altaba A. Gli2 functions in FGF signaling during antero-posterior patterning. Development. 127:2000;4395-4405.
152. Frank-Kamenetsky M., Zhang X.M., Bottega S., Guicherit O., Wichterle H., Dudek H., Bimcrot D.F.Y., Wang S., Jones J., Shulok L.L., Rubin J.A. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. J. Biol. 1:(1):2002;10.
153. Chen J.K., Taipale J., Young E.K., Maiti T., Bichy P.A. Small molecule modulation of Smoothened activity. Proc. Natl. Acad. Sci. USA. 99:2002;14071-14076.
154. Jia J., Amanai K., Wang G., Tang J., Wang B., Jiang J. Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus. Nature. 41:2002;548-552.
155. Price M.A., Kalderon D. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase3 and Casein Kinase 1. Cell. 108:2002;823-835.