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.
Hsiang
Chin-Hui
CH
Department of Urology, University of California, Irvine, California, USA.
Tunoda
Toshiyuki
T
Whang
Young E
YE
Tyson
Darren R
DR
Ornstein
David K
DK
D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D017305:Annexin A1; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D013755:Tetradecanoylphorbol Acetate