The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells

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.