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p66 Shc protein is upregulated by steroid hormones in hormone‐sensitive cancer cells and in primary prostate carcinomas
Author(s) -
Lee MingShyue,
Igawa Tsukasa,
Chen SiuJu,
Van Bemmel Dana,
Lin Jamie S.,
Lin FenFen,
Johansson Sonny L.,
Christman Judith K.,
Lin MingFong
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11621
Subject(s) - prostate cancer , lncap , cancer research , medicine , endocrinology , prostate , carcinogenesis , androgen , biology , downregulation and upregulation , cell growth , cancer cell , cancer , hormone , biochemistry , genetics , gene
Members of Shc family conventionally serve as critical adaptors in tyrosine phosphorylation signal transduction pathways. p66 Shc protein, a member of Shc family, is predominantly expressed in epithelial cells, whereas the regulation of its expression remains an enigma. We describe the effect of steroid hormones on the protein level of p66 Shc and growth stimulation in hormone‐sensitive human prostate, testicular and breast cancer cells. In DHT‐treated androgen‐sensitive prostate cancer LNCaP C‐33 cells, the protein level of p66 Shc was elevated by approximately 3‐fold, correlating with increased cell growth. This DHT effect on p66 Shc protein level and growth regulation was also observed in another androgen‐sensitive prostate cancer cell line MDA PCa2b as well as 2 testicular cancer cell lines, Tera‐1 and Tera‐2 cells. Similarly, the female sex hormone estrogen had a stimulating effect on p66 Shc protein level and proliferation in estrogen‐sensitive MCF‐7 breast cancer cells. The upregulation of p66 Shc protein level by DHT was competitively abolished by Casodex, an androgen antagonist used to treat prostate cancer. Moreover, immunohistochemical analyses showed that the p66 Shc protein level was significantly higher in primary prostate tumors than in adjacent non‐cancerous cells ( p < 0.05). The data collectively indicate that p66 Shc protein levels correlate with steroid hormone‐stimulated cell growth and prostate carcinogenesis. © 2003 Wiley‐Liss, Inc.