Abstract |
The transient receptor potential channel, subfamily V, member 6 (TRPV6), is strongly expressed in advanced prostate cancer and significantly correlates with the Gleason >7 grading, being undetectable in healthy and benign prostate tissues. However, the role of TRPV6 as a highly Ca(2+)-selective channel in prostate carcinogenesis remains poorly understood. Here, we report that TRPV6 is directly involved in the control of prostate cancer cell (LNCaP cell line) proliferation by decreasing: (i) proliferation rate; (ii) cell accumulation in the S-phase of cell cycle and (iii) proliferating cell nuclear antigen ( PCNA) expression. We demonstrate that the Ca(2+) uptake into LNCaP cells is mediated by TRPV6, with the subsequent downstream activation of the nuclear factor of activated T-cell transcription factor (NFAT). TRPV6-mediated Ca(2+) entry is also involved in apoptosis resistance of LNCaP cells. Our results suggest that TRPV6 expression in LNCaP cells is regulated by androgen receptor, however, in a ligand-independent manner. We conclude that the upregulation of TRPV6 Ca(2+) channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.
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Authors | V Lehen'kyi, M Flourakis, R Skryma, N Prevarskaya |
Journal | Oncogene
(Oncogene)
Vol. 26
Issue 52
Pg. 7380-5
(Nov 15 2007)
ISSN: 1476-5594 [Electronic] England |
PMID | 17533368
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium Channels
- Enzyme Inhibitors
- NFATC Transcription Factors
- TRPV Cation Channels
- TRPV6 protein, human
- Thapsigargin
- Calcium
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Topics |
- Apoptosis
- Calcium
(metabolism)
- Calcium Channels
(genetics, metabolism)
- Calcium Signaling
- Cell Proliferation
- Enzyme Inhibitors
(pharmacology)
- Humans
- Male
- NFATC Transcription Factors
(metabolism)
- Prostatic Neoplasms
(genetics, metabolism)
- S Phase
(physiology)
- Signal Transduction
- TRPV Cation Channels
(genetics, metabolism)
- Thapsigargin
(pharmacology)
- Tumor Cells, Cultured
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