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EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen‐sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)
Author(s) -
Bonaccorsi Lorella,
Carloni Vinicio,
Muratori Monica,
Formigli Lucia,
Zecchi Sandra,
Forti Gianni,
Baldi Elisabetta
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20362
Subject(s) - androgen receptor , lncap , transfection , signal transduction , epidermal growth factor , cancer research , biology , androgen , internalization , epidermal growth factor receptor , cell culture , microbiology and biotechnology , prostate cancer , receptor , chemistry , endocrinology , medicine , cancer , hormone , biochemistry , genetics
We previously demonstrated that expression of androgen receptor (AR) by transfection of the androgen‐independent prostate cancer cell line PC3 decreases invasion and adhesion of these cells (PC3‐AR) through modulation of α6β4 integrin expression. The treatment with androgens further reduced invasion of the cells without modifying α6β4 expression, suggesting an interference with the invasion process by androgens. Here, we investigated EGF‐mediated signal transduction processes that lead to invasion in PC3‐AR cells. We show that EGF‐induced EGFR autotransphosphorylation is reduced in PC3‐AR cells compared to PC3 cells transfected only with the vector (PC3‐Neo). EGF‐stimulated PI3K activity, a key signaling pathway for invasion of these cells, and EGF‐PI3K interaction are also decreased in PC3‐AR cells and further reduced by treatment with androgen. Finally, we show that EGFR internalization process was reduced in PC3‐AR and LNCaP cells compared to PC3‐Neo. Investigations on the location of AR in PC3‐AR transfected cells were also conducted. Immunoconfocal microscopy and coimminoprecipitation studies demonstrated the presence of an interaction between EGFR and AR at membrane level in PC3‐AR and LNCaP cells. In conclusion, our results suggest that the expression of AR by transfection in PC3 cells confers a less‐malignant phenotype by interfering with EGFR signaling leading to invasion through a mechanism involving an interaction between AR and EGFR. © 2004 Wiley‐Liss, Inc.