Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signaling

Molecular Cancer

Volumn 9, Issue , 2010, Pages

  Hong, Seung Beom ^a   Oh, HyoungBin ^a   Valera, Vladimir A ^a   Stull, Jaime ^a   Ngo, Duy Tan ^a   Baba, Masaya ^a   Merino, Maria J ^a   Linehan, W Marston ^a   Schmidt, Laura S ^a,b  

^a NATIONAL CANCER INSTITUTE   (United States)

^b SAIC FREDERICK INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN A; ESTRONE; GREMLIN; INHIBIN A; INHIBITOR PROTEIN; SMAD3 PROTEIN; SMAD7 PROTEIN; THROMBOSPONDIN 1; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA2; UNCLASSIFIED DRUG; FLCN PROTEIN, HUMAN; ONCOPROTEIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIRT HOGG DUBE SYNDROME; CANCER CELL CULTURE; CANCER GROWTH; CARCINOGENESIS; CONTROLLED STUDY; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; KIDNEY CANCER; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; TUMOR SUPPRESSOR GENE; WILD TYPE; ANIMAL; DNA MICROARRAY; GENE VECTOR; GENETICS; KIDNEY TUMOR; LENTIVIRINAE; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

MUS MUSCULUS;

ANIMALS; CELL LINE, TUMOR; GENE EXPRESSION REGULATION; GENES, TUMOR SUPPRESSOR; GENETIC VECTORS; HUMANS; KIDNEY NEOPLASMS; LENTIVIRUS; MICE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTO-ONCOGENE PROTEINS; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA; TUMOR SUPPRESSOR PROTEINS;

EID: 77953719290     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-9-160     Document Type: Article

References (41)

1. Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol 1977, 113:1674-1677. 10.1001/archderm.113.12.1674, 596896.
2. Toro JR, Glenn G, Duray P, Darling T, Weirich G, Zbar B, Linehan M, Turner ML. Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia. Arch Dermatol 1999, 135:1195-1202. 10.1001/archderm.135.10.1195, 10522666.
3. Zbar B, Alvord WG, Glenn G, Turner M, Pavlovich CP, Schmidt L, Walther M, Choyke P, Weirich G, Hewitt SM, Duray P, Gabril F, Greenberg C, Merino MJ, Toro J, Linehan WM. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dube syndrome. Cancer Epidemiol Biomarkers Prev 2002, 11:393-400.
4. Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome. Am J Hum Genet 2005, 76:1023-1033. 10.1086/430842, 1196440, 15852235.
5. Toro JR, Wei MH, Glenn G, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino MJ, Pinto PA, Steinberg SM, Schmidt LS, Linehan WM. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube Syndrome: A new series of 50 families and a review of published reports. J Med Genet 2008, 45:321-331. 10.1136/jmg.2007.054304, 2564862, 18234728.
6. Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dube syndrome. Am J Surg Pathol 2002, 26:1542-1552. 10.1097/00000478-200212000-00002, 12459621.
7. Khoo SK, Bradley M, Wong FK, Hedblad MA, Nordenskjold M, Teh BT. Birt-Hogg-Dube syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2. Oncogene 2001, 20:5239-5242. 10.1038/sj.onc.1204703, 11526515.
8. Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, Turner ML, Duray P, Merino M, Hewitt S, Pavlovich CP, Glenn G, Greenberg CR, Linehan WM, Zbar B. Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet 2001, 69:876-882. 10.1086/323744, 1226073, 11533913.
9. Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2002, 2:157-164. 10.1016/S1535-6108(02)00104-6, 12204536.
10. Khoo SK, Giraud S, Kahnoski K, Chen J, Motorna O, Nickolov R, Binet O, Lambert D, Friedel J, Lévy R, Ferlicot S, Wolkenstein P, Hammel P, Bergerheim U, Hedblad MA, Bradley M, Teh BT, Nordenskjöld M, Richard S. Clinical and genetic studies of Birt-Hogg-Dube syndrome. J Med Genet 2002, 39:906-912. 10.1136/jmg.39.12.906, 1757219, 12471204.
11. Leter EM, Koopmans AK, Gille JJ, van OSTA, Vittoz GG, David EF, Jaspars EH, Postmus PE, van Moorselaar RJ, Craanen ME, Starink TM, Menko FH. Birt-Hogg-Dube syndrome: clinical and genetic studies of 20 families. J Invest Dermatol 2008, 128:45-49. 10.1038/sj.jid.5700959, 17611575.
12. Vocke CD, Yang Y, Pavlovich CP, Schmidt LS, Nickerson ML, Torres-Cabala CA, Merino MJ, Walther MM, Zbar B, Linehan WM. High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dube-associated renal tumors. J Natl Cancer Inst 2005, 97:931-935. 10.1093/jnci/dji154, 15956655.
13. Okimoto K, Sakurai J, Kobayashi T, Mitani H, Hirayama Y, Nickerson ML, Warren MB, Zbar B, Schmidt LS, Hino O. A germ-line insertion in the Birt-Hogg-Dube (BHD) gene gives rise to the Nihon rat model of inherited renal cancer. Proc Natl Acad Sci USA 2004, 101:2023-2027. 10.1073/pnas.0308071100, 357045, 14769940.
14. Lingaas F, Comstock KE, Kirkness EF, Sorensen A, Aarskaug T, Hitte C, Nickerson ML, Moe L, Schmidt LS, Thomas R, Breen M, Galibert F, Zbar B, Ostrander EA. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Hum Mol Genet 2003, 12:3043-3053. 10.1093/hmg/ddg336, 14532326.
15. Baba M, Furihata M, Hong SB, Tessarollo L, Haines DC, Southon E, Patel V, Igarashi P, Alvord WG, Leighty R, Yao M, Bernardo M, Ileva L, Choyke P, Warren MB, Zbar B, Linehan WM, Schmidt LS. Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys. J Natl Cancer Inst 2008, 100:140-154. 10.1093/jnci/djm288, 2704336, 18182616.
16. Chen J, Futami K, Petillo D, Peng J, Wang P, Knol J, Li Y, Khoo SK, Huang D, Qian CN, Zhao P, Dykema K, Zhang R, Cao B, Yang XJ, Furge K, Williams BO, Teh BT. Deficiency of FLCN in mouse kidney led to development of polycystic kidneys and renal neoplasia. PLoS One 2008, 3:e3581. 10.1371/journal.pone.0003581, 2570491, 18974783.
17. Hasumi Y, Baba M, Ajima R, Hasumi H, Valera VA, Klein ME, Haines DC, Merino MJ, Hong SB, Yamaguchi TP, Schmidt LS, Linehan WM. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci USA 2009, 106:18722-18727. 10.1073/pnas.0908853106, 2765925, 19850877.
18. Hartman TR, Nicolas E, Klein-Szanto A, Al Saleem T, Cash TP, Simon MC, Henske EP. The role of the Birt-Hogg-Dube protein in mTOR activation and renal tumorigenesis. Oncogene 2009, 28:1594-1604. 10.1038/onc.2009.14, 2664853, 19234517.
19. Hudon V, Sabourin S, Dydensborg AB, Kottis V, Ghazi A, Paquet M, Crosby K, Pomerleau V, Uetani N, Pause A. Renal tumor suppressor function of the Birt-Hogg-Dube syndrome gene product folliculin. J Med Genet 2010, 47:182-189. 10.1136/jmg.2009.072009, 19843504.
20. Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR, Linehan WM, Schmidt LS, Zbar B. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci USA 2006, 103:15552-15557. 10.1073/pnas.0603781103, 1592464, 17028174.
21. Hasumi H, Baba M, Hong SB, Hasumi Y, Huang Y, Yao M, Valera VA, Linehan WM, Schmidt LS. Identification and characterization of a novel folliculin-interacting protein FNIP2. Gene 2008, 415:60-67. 10.1016/j.gene.2008.02.022, 2727720, 18403135.
22. van Slegtenhorst M, Khabibullin D, Hartman TR, Nicolas E, Kruger WD, Henske EP. The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe. J Biol Chem 2007, 282:24583-24590. 10.1074/jbc.M700857200, 17556368.
23. Yang Y, Padilla-Nash HM, Vira MA, Abu-Asab MS, Val D, Worrell R, Tsokos M, Merino MJ, Pavlovich CP, Ried T, Linehan WM, Vocke CD. The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dube gene pathway. Cancer Genet Cytogenet 2008, 180:100-109. 10.1016/j.cancergencyto.2007.10.010, 2440670, 18206534.
24. Singh SR, Zhen W, Zheng Z, Wang H, Oh SW, Liu W, Zbar B, Schmidt LS, Hou SX. The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance. Oncogene 2006, 25:5933-5941. 10.1038/sj.onc.1209593, 16636660.
25. Derynck R, Feng XH. TGF-beta receptor signaling. Biochim Biophys Acta 1999, 1333:F105-150.
26. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003, 113:685-700. 10.1016/S0092-8674(03)00432-X, 12809600.
27. de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst 2000, 92:1388-1402. 10.1093/jnci/92.17.1388, 10974075.
28. Markowitz S, Wang J, Myeroff L, Parsons R, Sin L, Lutterbaugh J. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995, 268:1336-1338. 10.1126/science.7761852, 7761852.
29. Parsons R, Myeroff LL, Liu B, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B. Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res 1995, 55:5548-5550.
30. Lu SL, Akiyama Y, Nagasaki H, Saitoh K, Yuasa Y. Mutations of the transforming growth factor-beta type II receptor gene and genomic instability in hereditary nonpolyposis colorectal cancer. Biochem Biophys Res Commun 1995, 216:452-457. 10.1006/bbrc.1995.2644, 7488133.
31. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996, 271:350-353. 10.1126/science.271.5247.350, 8553070.
32. MacGrogan D, Pegram M, Slamon D, Bookstein R. Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. Oncogene 1997, 15:1111-1114. 10.1038/sj.onc.1201232, 9285566.
33. Han SU, Kim HT, Seong DH. Loss of the Smad3 expression increases susceptibility to tumorigenicity in human gastric cancer. Oncogene 2004, 23:1333-1341. 10.1038/sj.onc.1207259, 14647420.
34. Takagi Y, Kohmura H, Futamura M, Kida H, Tanemura H, Shimokawa K, Saji S. Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. Gastroenterology 1996, 111:1369-1372. 10.1053/gast.1996.v111.pm8898652, 8898652.
35. Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY. Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp Biol Med (Maywood.) 2006, 231:534-544.
36. Maeshima A, Miya M, Mishima K, Yamashita S, Kojima I, Nojima Y. Activin A: autocrine regulator of kidney development and repair. Endocr J 2008, 55:1-9. 10.1507/endocrj.KR-113, 17827789.
37. Ioachim E, Michael MC, Salmas M, Damala K, Tsanou E, Michael MM, Malamou-Mitsi V, Stavropoulos NE. Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer 2006, 6:140. 10.1186/1471-2407-6-140, 1538616, 16732887.
38. Sutton CD, O'Byrne K, Goddard JC, Marshall LJ, Jones L, Garcea G, Dennison AR, Poston G, Lloyd DM, Berry DP. Expression of thrombospondin-1 in resected colorectal liver metastases predicts poor prognosis. Clin Cancer Res 2005, 11:6567-6573. 10.1158/1078-0432.CCR-05-0439, 16166434.
39. Rice AJ, Steward MA, Quinn CM. Thrombospondin 1 protein expression relates to good prognostic indices in ductal carcinoma in situ of the breast. J Clin Pathol 2002, 55:921-925. 10.1136/jcp.55.12.921, 1769827, 12461058.
40. Guerrero D, Guarch R, Ojer A, Casas JM, Ropero S, Mancha A, Pesce C, Lloveras B, Garcia-Bragado F, Puras A. Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma. BJU Int 2008, 102:747-755. 10.1111/j.1464-410X.2008.07603.x, 18336597.
41. Rozen S, Skaletsky H. Primer3 on the www for general users and for biologist programmers. Methods Mol Biol 2000, 132:365-386.