Calreticulin expression is associated with androgen regulation of the sensitivity to calcium ionophore-induced apoptosis in LNCaP prostate cancer cells.
Calreticulin has been identified previously as one of the androgen-response genes in the prostate. The role of calreticulin in androgen action was studied using androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate cancer cell lines. Calreticulin appears to be a primary androgen-response gene in cultured LNCaP cells because androgen induction of calreticulin mRNA resists protein synthesis inhibition. Calreticulin is a high capacity intracellular Ca2+ binding protein, suggesting that calreticulin expression is likely to be associated with the intracellular Ca2+ buffering capacity that could regulate the sensitivity to cytotoxic intracellular Ca2+ overload. As expected, androgen protects androgen-sensitive LNCaP but not androgen-insensitive PC-3 cells from cytotoxic intracellular Ca2+ overload induced by Ca2+ ionophore A23187. To provide evidence for the role of calreticulin in reducing cytotoxic effect of Ca2+ influx in prostatic cells, we have shown that calreticulin antisense oligonucleotide down-regulates calreticulin protein level and significantly increases the sensitivity to A23187-induced apoptosis in both LNCaP and PC-3 cells. Furthermore, calreticulin antisense oligonucleotide reverses the androgen-induced resistance to A23187 in LNCaP cells. The above observations collectively suggest that calreticulin mediates androgen regulation of the sensitivity to Ca2+ ionophore-induced apoptosis in LNCaP cells.
Zhu
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Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Wang
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D000728:Androgens / Q000378:metabolism*; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D037282:Calreticulin; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012261:Ribonucleoproteins / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D007476:Ionophores; D016376:Oligonucleotides, Antisense; D012261:Ribonucleoproteins; D000001:Calcimycin; D002118:Calcium