Evidence that Sp1 positively and Sp3 negatively regulate and androgen does not directly regulate functional tumor suppressor 15-lipoxygenase 2 (15-LOX2) gene expression in normal human prostate epithelial cells

Oncogene
Shaohua TangDean G Tang

Abstract

In this project, we studied the gene regulation of 15-lipoxygenase 2 (15-LOX2), the most abundant arachidonate-metabolizing LOX in adult human prostate and a negative cell-cycle regulator in normal human prostate (NHP) epithelial cells. Through detailed in silico promoter examination and promoter deletion and activity analysis, we found that several Sp1 sites (i.e., three GC boxes and one CACCC box) in the proximal promoter region play a critical role in regulating 15-LOX2 expression in NHP cells. Several pieces of evidence further suggest that the Sp1 and Sp3 proteins play a physiologically important role in positively and negatively regulating the 15-LOX2 gene expression, respectively. First, mutations in the GC boxes affected the 15-LOX2 promoter activity. Second, both Sp1 and Sp3 proteins were detected in the protein complexes that bound the GC boxes revealed by electrophoretic mobility shift assay. Third, importantly, inhibition of Sp1 activity or overexpression of Sp3 both inhibited the endogenous 15-LOX2 mRNA expression. Since 15-LOX2 is normally expressed in the prostate luminal epithelial cells, we subsequently explored whether androgen/androgen receptor may directly regulate its gene expression. The results indicate t...Continue Reading

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Citations

Nov 11, 2005·Molecular Biology of the Cell·Fang LiuGary D Kao
Aug 13, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Bao-sheng WangYi Zhao
Aug 25, 2015·Redox Biology·Ryuichi Mashima, Torayuki Okuyama
Dec 18, 2008·International Journal of Cancer. Journal International Du Cancer·Yong TangDaotai Nie
Dec 7, 2007·International Journal of Cancer. Journal International Du Cancer·Bobby BhatiaDean G Tang
Oct 8, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Stephen Safe, Maen Abdelrahim
Oct 16, 2014·Biochimica Et Biophysica Acta·Hartmut KuhnKlaus van Leyen
Apr 16, 2014·Cell Cycle·Mahipal V SuraneniDean G Tang
Feb 22, 2011·Free Radical Biology & Medicine·Huan Qiao, James M May
Dec 2, 2014·Progress in Lipid Research·Thomas HornDagmar Heydeck
Mar 24, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ping HuaFayez K Ghishan
Jul 25, 2019·Frontiers in Pharmacology·Ryan G Snodgrass, Bernhard Brüne

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