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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 646 - 652 (7page)
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Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens.
STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However,the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-α is able to regulate gene transcription of STS, we studied the effect of TNF-α on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-α significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-α resulted in a strong increase in the phosphorylation of Akt on Ser-473 and when cells were treated with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV), induction of STS mRNA expression by TNF-α was significantly prevented.
Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-α-mediated STS induction. We also found that TNF-α is able to increase STS mRNA expression in other human cancer cells such as LNCaP, MDA-MB-231,and MCF-7 as well as PC-3 cells. Taken together, our results strongly suggest that PI 3-kinase/Akt activation mediates induction of human STS gene expression by TNF-α in human cancer cells.
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참고문헌 (25)
참고문헌 신청
[학
Dao TL / 1974 / Steroid sulfatase activities in human breast tumors / Proc Soc Exp Biol Med 146 : 381 ~ 384
Feldman RI / 2005 / Novel small molecule inhibitors of 3-phosphoinositide- dependent kinase-1 / J Biol Chem 280 : 19867 ~ 19874
Foster PA / 2008 / The use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer / Endocrinology 149 : 4035 ~ 4042
Hernandez-Martin A / 1999 / De Unamuno P. X-linked ichthyosis: an update / Br J Dermatol 141 : 617 ~ 627
Dao TL / 1974 / Steroid sulfatase activities in human breast tumors / Proc Soc Exp Biol Med 146 : 381 ~ 384
Feldman RI / 2005 / Novel small molecule inhibitors of 3-phosphoinositide- dependent kinase-1 / J Biol Chem 280 : 19867 ~ 19874
Foster PA / 2008 / The use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer / Endocrinology 149 : 4035 ~ 4042
Hernandez-Martin A / 1999 / De Unamuno P. X-linked ichthyosis: an update / Br J Dermatol 141 : 617 ~ 627
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