INVOLVEMENT OF SHC IN THE SIGNALING RESPONSE OF HUMAN PROSTATE TUMOR-CELL LINES TO EPIDERMAL GROWTH-FACTOR

Autocrine growth factors for the epidermal growth factor receptor (EGF R) have been identified in prostate tumors, implicating a role for EGF R in the progression of prostate cancer. To investigate early signalin g mechanisms used by the EGFR in prostate tumor cells, we have charact erized the involvement of the Shc (src homology 2/x-collagen related) adapter protein in EGFR signaling in several human prostate tumor cell lines. In androgen-responsive lymph node prostate cancer (LNCaP) cell s and androgen-insensitive PC3, DU145 and PPC-1 cells, Shc was identif ied as one of the most prominent phosphotyrosine proteins to be elevat ed in response to EGF. Equivalent levels of the 46- and 52-kDa Shc iso forms were detected in all of the tumor cell lines tested. However, le vels of the 66-kDa isoform were variable among the cell lines. In all of the tumor cell lines, EGF caused an association between Shc and Grb 2, another adapter protein linked to cellular ras activation. Addition ally, several phosphotyrosine proteins, including a 115-120-kDa protei n in EGF-treated LNCaP cells, co-associated with Shc. The profile of t hese Shc-associating proteins, however, differed among the tumor cell lines. Our results indicate that Shc is a common downstream element of EGFR signaling in prostate tumor cells and suggest multiple functions for Shc in prostate tumorigenesis. (C) 1998 Wiley-Liss, Inc.