Tyrosine-317 of p52Shc mediates androgen-stimulated proliferation signals in human prostate cancer cells

Ming Shyue Lee, Tsukasa Igawa, Ming Fong Lin

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The involvement of tyrosine phosphorylation signaling pathways in steroid-induced cell proliferation has received much attention. However, the adaptor molecule that mediates this interaction remains to be identified. In this communication, we identify p52Shc as the mediator between tyrosine phosphorylation signaling and steroid signaling in steroid-responsive cell proliferation. Although the different LNCaP prostate cancer cells, C-33, C-51 and C-81, express similar levels of functional androgen receptor (AR), they exhibit different levels of androgen sensitivity. C-33 cell proliferation is highly responsive to the presence of androgens, whereas C-51 cell proliferation is comparatively less responsive to androgens. In contrast, C-81 cell proliferation is independent of androgens. In these cells, tyrosine phosphorylation levels of both p52Shc and ErbB-2 were greatest in C-81 cells, comparatively less in C-51 cells and weaker in C-33 cells. The levels and activity of protein tyrosine phosphatase, cellular prostatic acid phosphatase, decreased correspondingly in those cells. In both androgen-independent, rapidly growing C-81 and ErbB-2 cDNA-transfected C-33 cells, p52Shc was hyperphosphorylated at Tyr317 (Y317). Conversely, p52Shc tyrophosphorylation was decreased in prostatic acid phosphatase cDNA-transfected stable subclones of C-81 cells, which restore androgen-sensitive proliferation and leads to slow growth rates. In C-33 cells, androgen-stimulated cell proliferation correlated with tyrophosphorylation of ErbB-2 and increased phosphorylation of p52Shc at Y317, but not at Y239, differing from phosphorylation patterns associated with epidermal growth factor (EGF) stimulation. Furthermore, overexpression of a mutant of p52 Shc, that is Y317F, blocks Y317 phosphorylation of endogenous p52Shc and abolishes androgen-stimulated proliferation, but not EGF-stimulated proliferation. Thus, Y317 of p52Shc serves as an important regulatory site that allows tyrosine phosphorylation pathways to moderate androgen sensitivity in human prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)3048-3058
Number of pages11
Issue number17
StatePublished - Apr 15 2004


  • Androgen sensitivity
  • ErbB-2
  • Human prostate cancer
  • PAcP
  • p52

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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