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Induction of steroid sulfatase expression in PC-3 human prostate cancer cells by insulin-like growth factor II.

Abstract：

:Human steroid sulfatase (STS) plays an important role in regulating the formation of biologically active estrogens and may be a promising target for treating estrogen-mediated carcinogenesis. The molecular mechanism of STS gene expression, however, is still not clear. Growth factors are known to increase STS activity but the changes in STS expression have not been completely understood. To determine whether insulin-like growth factor (IGF)-II can induce STS gene expression, the effects of IGF-II on STS expression were studied in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that IGF-II treatment significantly increased the expression of STS mRNA and protein in concentration- and time-dependent manners. To understand the signaling pathway by which IGF-II induces STS gene expression, the effects of specific PI3-kinase/Akt and NF-κB inhibitors were determined. When the cells were treated with IGF-II and PI3-kinase/Akt inhibitors, such as LY294002, wortmannin, or Akt inhibitor IV, STS expression induced by IGF-II was significantly blocked. Moreover, we found that NF-κB inhibitors, such as MG-132, bortezomib, Bay 11-7082 or Nemo binding domain (NBD) binding peptide, also strongly prevented IGF-II from inducing STS gene expression. We assessed whether IGF-II activates STS promoter activity using transient transfection with a luciferase reporter. IGF-II significantly stimulated STS reporter activity. Furthermore, IGF-II induced expression of 17β-hydroxysteroid dehydrogenase (HSD) 1 and 3, whereas it reduced estrone sulfotransferase (EST) gene expression, causing enhanced estrone and β-estradiol production. Taken together, these results strongly suggest that IGF-II induces STS expression via a PI3-kinase/Akt-NF-κB signaling pathway in PC-3 cells and may induce estrogen production and estrogen-mediated carcinogenesis.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Sung CH,Im HJ,Park N,Kwon Y,Shin S,Ye DJ,Cho NH,Park YS,Choi HK,Kim D,Chun YJ

doi

10.1016/j.toxlet.2013.09.006

subject

Has Abstract

pub_date

2013-11-25 00:00:00

pages

109-15

issue

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(13)01313-1

journal_volume

223

pub_type

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Induction of steroid sulfatase expression in PC-3 human prostate cancer cells by insulin-like growth factor II.