Expression and Function of ATIP/MTUS1 in Human Prostate Cancer Cell Lines

Autor: Simon N S Louis, Albert G Frauman, William J. Louis, Laurie T C Chow, Michael A Krezel, Linda Adriana Rezmann, Kevin J. Catt, Christos Tikellis
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Popis: BACKGROUND We have previously demonstrated Ang II type 2 (AT2-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines. METHODS To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT2-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [3H]thymidine incorporation assays. RESULTS The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT2-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells. CONCLUSIONS The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT2-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT2-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression. Prostate 70: 1563–1574, 2010. © 2010 Wiley-Liss, Inc.
Databáze: OpenAIRE