PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells

被引:127
作者
Zhao, H [1 ]
Dupont, J [1 ]
Yakar, S [1 ]
Karas, M [1 ]
LeRoith, D [1 ]
机构
[1] NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA
关键词
PTEN; IGF-IR; prostate cancer; protein synthesis; apoptosis;
D O I
10.1038/sj.onc.1207162
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PTEN is a tumor suppressor gene that is frequently mutated in human tumors. It functions primarily as a lipid phosphatase and plays a key role in the regulation of phosphatidylinositol-3'-kinase. PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5) P3, a phospholipid that activates AKT, a central regulator of apoptosis. To understand the role of PTEN in regulating cell proliferation and apoptosis, we stably overexpressed PTEN in PC3 cells, which are prostate cancer cells that lack PTEN. Overexpression of PTEN in two different clones inhibited cell proliferation and increased serum starvation-induced apoptosis, as compared to control cells. Interestingly, PTEN overexpression resulted in a 44 - 60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49 - 64% reduction in cell surface IGF-IR expression. [S-35] methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis.
引用
收藏
页码:786 / 794
页数:9
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