The tumor suppressor protein p150Sal2 in carcinogenesis
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The transcription factor p150Sal2, the product of the SALL2 gene, was first identified as a binding target of the oncogenic mouse polyomavirus T antigen. However, mouse polyomavirus is not the only oncogenic virus that targets p150Sal2; the human papillomavirus E6 protein also targets this cellular protein in order to overcome p150Sal2-mediated growth arrest. Studies have demonstrated that p150Sal2 recognizes GC-rich regions of the promoter and transcriptionally induces p21Cip1/Waf1 and BAX in human ovarian epithelial cancer cells, resulting in cell growth arrest and apoptosis. Although the p150Sal2 protein is strongly expressed in surface epithelial cells of the ovary, immunostaining experiments showed that expression of p150Sal2 was lost in 90 % of 210 human ovarian carcinomas, supporting an important tumor suppressive role for p150Sal2 in the human ovary. Mechanisms of silencing SALL2 in OVCA cell lines and primary tumors and possible therapeutic approaches for ovarian carcinoma are discussed in this review.
KeywordsMouse polyomavirus Human papillomavirus SALL2 Transcriptional targets Ovarian carcinoma Promoter methylation
This work was supported by a Texas A&M University-Kingsville Research Award (to CKS; 160330–00016) and the research fund of Hanyang University (HY-2014-N) to HY.
- 6.Yamaguchi YL, Tanaka SS, Kumagai M, Fujimoto Y, Terabayashi T, Matsui Y, Nishinakamura R: Sall4 is essential for mouse primordial germ cell specification by suppressing somatic cell program genes. Stem cells 2014Google Scholar
- 8.Liu J, Wang L, Yang A, Jiang P, Wang M. Up-regulation of SALL4 associated with poor prognosis in gastric cancer. Hepatogastroenterology. 2014;61:1459–64.Google Scholar
- 21.Imperiale MJ, Major, E.O.: Polyomaviruses; in Knipe DM, Howley, P.M. (ed) Fields virology. Philadelphia, PA, Lippincott Williams & Wilkins, 2007, vol 2, pp 2263–2298.Google Scholar
- 26.Gu H, Li D, Sung CK, Yim H, Troke P, Benjamin T: DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(sal2). Biochim Biophys Acta 2011Google Scholar