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The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells
Author(s) -
Hsiang ChinHui,
Tunoda Toshiyuki,
Whang Young E.,
Tyson Darren R.,
Ornstein David K.
Publication year - 2006
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.20457
Subject(s) - prostate cancer , annexin , lncap , signal transduction , cancer research , p38 mitogen activated protein kinases , apoptosis , kinase , annexin a5 , viability assay , mapk/erk pathway , biology , microbiology and biotechnology , cancer , medicine , biochemistry
BACKGROUND Although reduced expression levels of annexin I (ANX I) protein is a common finding in all stages of prostate cancer a causative relationship between ANX I dysregulation and prostate cancer development has yet to be established. METHODS Annexin I expression was restored in LNCaP and MDA PCa 2b that normally express low or undetectable levels of ANX I protein. The impact of restoring ANX I expression on cell viability, colony formation in soft agar, apoptosis, and extracellular signal‐regulated kinases (ERK), p38, c‐Jun N‐terminal kinases (JNK) activation was examined. RESULTS Restoring ANX I expression reduced cell viability, colony formation, in addition to inducing apoptosis. The proliferative response of epidermal growth factor was blocked by restoring ANX I expression. Furthermore, increasing basal and induced levels of phosphorylated p38 and JNK were observed in prostate cancer cells following restoration of ANX I expression. CONCLUSIONS Annexin I may have tumor suppressor functions in prostate cancer. The pro‐apoptotic effect of ANX I involves the activation of p38 and JNK, which appears to shift the balance of signal transduction away from proliferation and toward apoptosis. Prostate 66: 1413–1424, 2006. © 2006 Wiley‐Liss, Inc.