Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines
Open Access
- 1 October 1997
- journal article
- Published by Springer Nature in British Journal of Cancer
- Vol. 76 (7) , 884-889
- https://doi.org/10.1038/bjc.1997.479
Abstract
To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of G1-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10(-7) mol l(-1) 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells (Hs 766T and Capan-1), no such changes were observed. In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G1/S transition and induce growth inhibition in responsive cells.Keywords
This publication has 33 references indexed in Scilit:
- Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell linesGastroenterology, 1996
- Joining the complex: Cyclin-dependent kinase inhibitory proteins and the cell cycleCell, 1994
- Stifled by inhibitionsNature, 1994
- p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.Genes & Development, 1994
- p21 is a universal inhibitor of cyclin kinasesNature, 1993
- A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4Nature, 1993
- WAF1, a potential mediator of p53 tumor suppressionCell, 1993
- Growth Inhibition of Human Keratinocytes by 1,25-Dihydroxyvitamin D3 Is Linked to Dephosphorylation of Retinoblastoma Gene ProductBiochemical and Biophysical Research Communications, 1993
- Synthetic analogues of vitamin D3 with an oxygen atom in the side chain skeleton A trial of the development of vitamin D compounds which exhibit potent differentiation‐inducing activity without inducing hypercalcemiaFEBS Letters, 1987
- Synthetic studies of vitamin D3 analogues. VIII Synthesis of 22-oxavitamin D3 analogues.CHEMICAL & PHARMACEUTICAL BULLETIN, 1986