Premium
MEX3D is an oncogenic driver in prostate cancer
Author(s) -
Shao Longjiang,
Wang Jianghua,
Karatas Omer,
Ittmann Michael
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24216
Subject(s) - pten , prostate cancer , tmprss2 , cancer research , fusion gene , biology , prostate , cancer , tissue microarray , pathology , medicine , gene , pi3k/akt/mtor pathway , signal transduction , genetics , disease , covid-19 , infectious disease (medical specialty)
Background Prostate cancer (PCa) is the most common visceral malignancy and the second leading cause of cancer deaths in US men. The two most common genetic alterations in PCa are expression of the TMPRSS2/ERG (TE) fusion gene and loss of the PTEN tumor suppressor. These genetic alterations act cooperatively to transform prostatic epithelium but the exact mechanisms involved are unclear. Methods Microarray expression analysis of immortalized prostate epithelial cells transformed by loss of PTEN and expression of the TE fusion revealed MEX3D as one of the most highly upregulated genes. MEX3D expression in prostate cancer was examined in patient samples and in silico. In vitro and in vivo studies to characterize the biological impact of MEX3D were carried out. Analysis of the TCGA PanCancer database revealed TCF3 as a major target of MEX3D. The induction of TCF3 by MEX3D was confirmed and the biological impact of TCF3 examined by in vitro studies. Results MEX3D is expressed at increased levels in prostate cancer and is increased by decreased PTEN and/or expression of the TE fusion gene and drives soft agar colony formation, invasion and tumor formation in vivo . The known oncogenic transcription factor TCF3 is highly correlated with MEX3D in prostate cancer. MEX3D expression strongly induces TCF3, which promotes soft agar colony formation and invasion in vitro . Conclusions Loss of PTEN and expression of the TE fusion gene in prostate cancer strongly upregulates expression of MEX3D and its target TCF3 and promotes transformation associated phenotypes via this pathway.