p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas.
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.
Lee
Ming-Shyue
MS
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Igawa
Tsukasa
T
Chen
Siu-Ju
SJ
Van Bemmel
Dana
D
Lin
Jamie S
JS
Lin
Fen-Fen
FF
Johansson
Sonny L
SL
Christman
Judith K
JK
Lin
Ming-Fong
MF
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013736:Testicular Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D004967:Estrogens; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013196:Dihydrotestosterone