p150, product of the SALL2 gene, is a binding partner of the polyoma virus large T antigen and a putative tumor suppressor. p150 binds to the nuclease hypersensitive element of the c-MYC promoter and represses c-MYC transcription. Overexpression of p150 in human ovarian surface epithelial cells leads to decreased expression, and downregulation to increased expression, of c-MYC. c-MYC is repressed upon restoration of p150 to ovarian carcinoma cells. Induction of apoptosis by etoposide results in recruitment of p150 to the c-MYC promoter and to repression of c-MYC. Analysis of data in The Cancer Genome Atlas shows negative correlations between SALL2 and c-MYC expression in four common solid tumor types.
References
[1]
Howley PM, Livingston DM (2009) Small DNA tumor viruses: large contributors to biomedical sciences. Virology 384: 256–259.
[2]
Li D, Dower K, Ma Y, Tian Y, Benjamin TL (2001) A tumor host range selection procedure identifies p150(sal2) as a target of polyoma virus large T antigen. Proc Natl Acad Sci U S A 98: 14619–14624.
[3]
Parroche P, Touka M, Mansour M, Bouvard V, Thepot A, et al. (2011) Human papillomavirus type 16 E6 inhibits p21(WAF1) transcription independently of p53 by inactivating p150(Sal2). Virology 417: 443–448.
[4]
Sweetman D, Munsterberg A (2006) The vertebrate spalt genes in development and disease. Dev Biol 293: 285–293.
[5]
Kohlhase J, Chitayat D, Kotzot D, Ceylaner S, Froster UG, et al. (2005) SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal-ocular syndrome, and related disorders. Hum Mutat 26: 176–183.
[6]
Kohlhase J, Taschner PE, Burfeind P, Pasche B, Newman B, et al. (1999) Molecular analysis of SALL1 mutations in Townes-Brocks syndrome. Am J Hum Genet 64: 435–445.
[7]
Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, et al. (2002) Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet 71: 1195–1199.
[8]
Kiefer SM, Ohlemiller KK, Yang J, McDill BW, Kohlhase J, et al. (2003) Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects. Hum Mol Genet 12: 2221–2227.
[9]
Li D, Tian Y, Ma Y, Benjamin T (2004) p150(Sal2) is a p53-independent regulator of p21(WAF1/CIP). Mol Cell Biol 24: 3885–3893.
[10]
Ma Y, Li D, Chai L, Luciani AM, Ford D, et al. (2001) Cloning and characterization of two promoters for the human HSAL2 gene and their transcriptional repression by the Wilms tumor suppressor gene product. J Biol Chem 276: 48223–48230.
[11]
Gu H, Li D, Sung CK, Yim H, Troke P, et al. (2011) DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(Sal2). Biochim Biophys Acta 1809: 276–283.
[12]
Liu H, Adler AS, Segal E, Chang HY (2007) A transcriptional program mediating entry into cellular quiescence. PLoS Genet 3: e91.
[13]
Sung CK, Dahl J, Yim H, Rodig S, Benjamin TL (2011) Transcriptional and post-translational regulation of the quiescence factor and putative tumor suppressor p150(Sal2). FASEB J 25: 1275–1283.
[14]
Clauss A, Ng V, Liu J, Piao H, Russo M, et al. (2010) Overexpression of elafin in ovarian carcinoma is driven by genomic gains and activation of the nuclear factor kappaB pathway and is associated with poor overall survival. Neoplasia 12: 161–172.
[15]
Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, et al. (2005) Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 65: 2162–2169.
[16]
Nelson JD, Denisenko O, Bomsztyk K (2006) Protocol for the fast chromatin immunoprecipitation (ChIP) method. Nat Protoc 1: 179–185.
[17]
Gonzalez V, Hurley LH (2010) The c-MYC NHE III(1): function and regulation. Annu Rev Pharmacol Toxicol 50: 111–129.
[18]
Yang D, Hurley LH (2006) Structure of the biologically relevant G-quadruplex in the c-MYC promoter. Nucleosides Nucleotides Nucleic Acids 25: 951–968.
[19]
Shichiri M, Hanson KD, Sedivy JM (1993) Effects of c-myc expression on proliferation, quiescence, and the G0 to G1 transition in nontransformed cells. Cell Growth Differ 4: 93–104.
[20]
Trumpp A, Refaeli Y, Oskarsson T, Gasser S, Murphy M, et al. (2001) c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414: 768–773.
[21]
Hoffman B, Liebermann DA (2008) Apoptotic signaling by c-MYC. Oncogene 27: 6462–6472.
[22]
Ho JS, Ma W, Mao DY, Benchimol S (2005) p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol 25: 7423–7431.
[23]
Sachdeva M, Zhu S, Wu F, Wu H, Walia V, et al. (2009) p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 106: 3207–3212.
[24]
Murphy DJ, Junttila MR, Pouyet L, Karnezis A, Shchors K, et al. (2008) Distinct thresholds govern Myc's biological output in vivo. Cancer Cell 14: 447–457.
[25]
Soucek L, Evan GI (2010) The ups and downs of Myc biology. Curr Opin Genet Dev 20: 91–95.
[26]
Darcy KM, Brady WE, Blancato JK, Dickson RB, Hoskins WJ, et al. (2009) Prognostic relevance of c-MYC gene amplification and polysomy for chromosome 8 in suboptimally-resected, advanced stage epithelial ovarian cancers: a Gynecologic Oncology Group study. Gynecol Oncol 114: 472–479.
[27]
Haverty PM, Hon LS, Kaminker JS, Chant J, Zhang Z (2009) High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors. BMC Med Genomics 2: 21.
[28]
Gorringe KL, George J, Anglesio MS, Ramakrishna M, Etemadmoghadam D, et al. (2010) Copy number analysis identifies novel interactions between genomic loci in ovarian cancer. PLoS One 5.
[29]
Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma VM, et al. (2007) DNA profiling of primary serous ovarian and fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification. J Pathol 213: 46–55.
