p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas

Ming Shyue Lee, Tsukasa Igawa, Siu Ju Chen, Dana Van Bemmel, Jamie S. Lin, Fen Fen Lin, Sonny L. Johansson, Judith K. Christman, Ming Fong Lin

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Members of Shc family conventionally serve as critical adaptors in tyrosine phosphorylation signal transduction pathways. p66Shc 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 p66Shc 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 p66Shc was elevated by approximately 3-fold, correlating with increased cell growth. This DHT effect on p66Shc 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 p66Shc protein level and proliferation in estrogen-sensitive MCF-7 breast cancer cells. The upregulation of p66Shc protein level by DHT was competitively abolished by Casodex, an androgen antagonist used to treat prostate cancer. Moreover, immunohistochemical analyses showed that the p66Shc 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.

Original languageEnglish (US)
Pages (from-to)672-678
Number of pages7
JournalInternational Journal of Cancer
Volume108
Issue number5
DOIs
StatePublished - Feb 20 2004

Keywords

  • Breast cancer
  • Prostate cancer
  • Sex hormone
  • Testicular cancer
  • p66

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lee, M. S., Igawa, T., Chen, S. J., Van Bemmel, D., Lin, J. S., Lin, F. F., Johansson, S. L., Christman, J. K., & Lin, M. F. (2004). p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas. International Journal of Cancer, 108(5), 672-678. https://doi.org/10.1002/ijc.11621