p66^Shc protein is upregulated by steroid hormones in hormone‐sensitive cancer cells and in primary prostate carcinomas

Abstract

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Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells

“…To the best of our knowledge, this is the first report that p66Shc-ROS pathway mediates early androgenic cell proliferation in androgen-sensitive prostate cancer cells, which is independent of AR-dependent gene expression, such as PSA. Data obtained from this study, thus, provide a molecular explanation for the clinical observations on increased p66Shc and ROS production in archival prostate cancer specimens (Lee et al, 2004a;Lim et al, 2005). In parallel, increased levels of H 2 O 2 -producing enzymes, such as Nox1 and SOD, are also noticed in prostate cancer specimens (Kuruma et al, 2005;Lim et al, 2005).…”

“…p66Shc regulates DHT-induced proliferation in prostate cancer cells Previous studies indicated that p66Shc, which increases intracellular ROS levels, is elevated in DHT-treated prostate cancer cells (Lee et al, 2004a; Figure 3a). Furthermore, semiquantitative analyses of the blots indicated a significantly higher level of p66Shc protein from 8 h of DHT treatment (Po0.05) (Supplementary Figure 1) prior to increase in ROS production (16 h), as indicated by an dichlorofluorescein diacetate (DCF-DA) fluorescence (Figure 3b), and the stimulation of cell proliferation, as indicated by the increase in Cyclin D1 level (24 h) (Figure 3a), the percentage of cells at S-phase (24 h) ( Figure 3c) and cell number (48 h) (Figure 3d).…”

“…In prostate cancer cell lines, p66Shc protein level positively correlates with their growth rates (Lee et al, 2004a;Veeramani et al, 2005). Importantly, growth stimulation of prostate, testis and breast cancer cell lines with steroid hormones is accompanied by an increase in p66Shc protein level (Lee et al, 2004a), implying its function in steroid-induced proliferation. Thus, the biological outcome of p66Shc signaling might be diverse in different cell types.…”

“…Prostate carcinoma tissues display higher p66Shc protein levels in the cancerous cells than the adjacent non-cancerous cells (Lee et al, 2004a). In prostate cancer cell lines, p66Shc protein level positively correlates with their growth rates (Lee et al, 2004a;Veeramani et al, 2005). Importantly, growth stimulation of prostate, testis and breast cancer cell lines with steroid hormones is accompanied by an increase in p66Shc protein level (Lee et al, 2004a), implying its function in steroid-induced proliferation.…”

“…However, a negative correlation between p66Shc and tumorigenicity in breast cancer tissues has been reported recently, and further studies are thus required to define its role in breast carcinogenesis (Stevenson and Frackelton, 1998;Davol et al, 2003). Prostate carcinoma tissues display higher p66Shc protein levels in the cancerous cells than the adjacent non-cancerous cells (Lee et al, 2004a). In prostate cancer cell lines, p66Shc protein level positively correlates with their growth rates (Lee et al, 2004a;Veeramani et al, 2005).…”