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

Hsiang CH, Tunoda T, Whang YE, Tyson DR, Ornstein DK
Prostate. 2006 66 (13): 1413-24

PMID: 16741918 · DOI:10.1002/pros.20457

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.

MeSH Terms (17)

Annexin A1 Apoptosis Cell Line Cell Line, Tumor Cell Proliferation Cell Survival Disease Progression Epidermal Growth Factor Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation, Neoplastic Humans Male MAP Kinase Kinase 4 p38 Mitogen-Activated Protein Kinases Prostatic Neoplasms Signal Transduction Tetradecanoylphorbol Acetate

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