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RhoC and guanine nucleotide exchange factor Net1 in androgen‐unresponsive mouse mammary carcinoma SC‐4 cells and human prostate cancer after short‐term endocrine therapy
Author(s) -
Kawata Hirotoshi,
Shimada Naoki,
Kamiakito Tomoko,
Komatsu Kenji,
Morita Tatsuo,
Ota Toshio,
Obayashi Masaya,
Shitara Kenya,
Tanaka Akira
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21511
Subject(s) - prostate cancer , rhoc , cancer research , biology , prostate , cancer , endocrinology , medicine , metastasis
BACKGROUND Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen‐dependent and androgen‐unresponsive SC‐3 and SC‐4 cells. METHODS Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC‐4 and SC‐3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay. The cell viability was analyzed with a Rho inhibitor or by stable transfection with either a dominant‐negative (DN) form of RhoC or a mutant form of NET1 (mutNET1). The expressions of RhoC, NET1, and epithelial–mesenchymal transition (EMT) markers were immunohistochemically analyzed in human prostate cancer specimens after short‐term endocrine therapy and in an untreated condition. RESULTS SC‐4 cells exhibited mesenchymal phenotypes with activation of Rho signals. Treatment with a Rho inhibitor suppressed the cell viability in SC‐4 cells, but not in SC‐3 cells. The cell viability of SC‐4 cells stably expressing DN‐RhoC and mutNET1 was also attenuated. In the immunohistochemical analysis, NET1 and the EMT marker of N‐cadherin were expressed at higher levels in prostate cancers after short‐term endocrine therapy than in untreated tumors, and RhoC expression was maintained after short‐term endocrine therapy. CONCLUSIONS Rho signaling is involved in the cell survival of SC‐4 cells. The higher expressions of RhoC and NET1 in human prostate cancers after short‐term endocrine therapy suggest that RhoC and NET1 may become therapeutic targets during endocrine therapy. Prostate 72:1071–1079, 2012. © 2011 Wiley Periodicals, Inc.