Activation of rapid signaling pathways does not contribute to 1 alpha,25-dihydroxyvitamin D3-induced growth inhibition of mouse prostate epithelial progenitor cells.
The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) inhibits the growth of prostate epithelial cells, however the underlying mechanisms have not been clearly delineated. In the current study, the impact of 1,25(OH)(2)D on the rapid activation of extracellular-regulated kinase (ERK) 1/2 and protein kinase C alpha (PKC alpha), and the role of these pathways in growth inhibition was examined in immortalized mouse prostate epithelial cells, MPEC3, that exhibit stem/progenitor cell characteristics. 1,25(OH)(2)D treatment suppressed the growth of MPEC3 in a dose and time dependent manner (e.g., 21% reduction at three days with 100 nM 1,25(OH)(2)D treatment). However, ERK1/2 activity was not altered by 100 nM 1,25(OH)(2)D treatment for time points from 1 min to 1 h in either serum-containing or serum-free medium. Similarly, PKC alpha activation (translocation onto the plasma membrane) was not regulated by short-term treatment of 100 nM 1,25(OH)(2)D. In conclusion, 1,25(OH)(2)D did not mediate rapid activation of ERK1/2 or PKC alpha in MPEC3 and therefore the growth inhibitory effect of 1,25(OH)(2)D is independent of rapid activation of these signaling pathways in this cell type.
Li
Jia
J
Interdepartmental Nutrition Program, Purdue University, 700 W. State Street, West Lafayette, Indiana 47907, USA.
Fleet
James C
JC
Teegarden
Dorothy
D
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011467:Prostate / Q000166:cytology* / Q000201:enzymology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3