Ca2+ dynamics in prostate cancer cells of increasing malignancy

This project investigates internal calcium dynamics in metastatic prostate cancer cell lines that mimic the progression of PCa to androgen resistance: (i) well differentiated LNCaP cells that require dihydrotestosterone (DHT) for survival, and (ii) poorly differentiated, highly aggressive PC3 and DU145 cells that are largely DHT-independent for their growth. [Ca2+]i measurements reveal important differences in the behavior of LnCaP cells and that of PC3 e DU145 cells. In androgen-independent prostate cancer (AIPC) cells, ATP induces a fast rise in intracellular Ca2+ which was entirely released from intracellular stores, was sensitive to phospholipase C (PLC) inhibitors and most probably due to the activation of P2Y receptors. In contrast, androgen-sensitive LnCaP cells do not respond to ATP challenge, suggesting a different functional purinergic receptor pro?le and sensitivity. This observation is in agreement with the previously reported hypothesis that purinergic receptors may represent a pharmacological target for prostate cancer treatment. A second significant difference it that AIPC PC3 and DU145 cells show a reduced capacity to store Ca2+ in thapsigargin-sensitive stores and limited store-operated calcium entry (SOCE), with respect to androgen-dependent LnCaP cells. The consequences of these differences will be discussed and interpreted with reference to previously proposed models for Ca2+ dependence of prostate carcinogenesis.

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