Role of stimulatory guanine nucleotide binding protein (GSalpha) in proliferation of PC-3M prostate cancer cells
| Autor: | J, Chien, G V, Shah |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Calcitonin
DNA Replication Male Time Factors Dose-Response Relationship Drug Nifedipine Blotting Western Colforsin 8-Bromo Cyclic Adenosine Monophosphate Prostatic Neoplasms Calcium Channel Blockers Transfection Verapamil GTP-Binding Proteins Cyclic AMP GTP-Binding Protein alpha Subunits Gs Tumor Cells Cultured Humans Electrophoresis Polyacrylamide Gel Calcium Channels Cell Division Protein Kinase C Adenylyl Cyclases Signal Transduction |
| Zdroj: | International journal of cancer. 91(1) |
| ISSN: | 0020-7136 |
| Popis: | Previous studies have shown that calcitonin-like immunoreactive substances are secreted by primary prostate cells. Furthermore, exogenously added calcitonin stimulates proliferation of androgen-responsive LnCaP cells. To examine the possible effect of calcitonin on growth of invasive prostate cancer cells, we tested its effects on proliferation of PC-3M cells. Calcitonin stimulated DNA synthesis of PC-3M cells in a dose-dependent fashion, and also stimulated adenylyl cyclase and protein kinase C activities. To further delineate the role of these signaling cascades in proliferation of PC-3M prostate cancer cells, we selectively activated these pathways by transfecting cDNAs expressing constitutively active forms of either Gsalpha (Gsalpha-QL) or Gqalpha (Gqalpha-QL). cDNAs expressing wild-type forms of G-proteins (Gsalpha-WT and Gqalpha-WT) were used as vehicle controls. Gqalpha-QL transfectants exhibited growth inhibition and terminal differentiation. Those expressing Gsalpha-QL exhibited a dramatic increase in growth rate. Gsalpha-QL transfectants displayed an almost 3-fold increase in [3H]-thymidine incorporation and over a 4-fold increase in growth rate when compared with parental PC-3M cells or those expressing wild-type Gsalpha (Gsalpha-WT). The growth-promoting action of Gsalpha-QL could not be mimicked by either 8-bromo cAMP or forskolin. However, nifedipine, a calcium channel antagonist, potently and selectively inhibited DNA synthesis in Gsalpha-QL transfectants. These results suggest that the growth-promoting actions of Gsalpha on PC-3M cells may be mediated by nifedipine-sensitive proliferative events. |
| Databáze: | OpenAIRE |
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