Cyclin-dependent Protein Research Articles

Arotinoid mofarotene (RO40-8757) up-regulates p21 and p27 during growth inhibition of pancreatic cancer cell lines.

Effective chemotherapy for pancreatic cancer is urgently needed. The anti-proliferative activity of a new retinoid, mofarotene (RO40-8757), was compared with that of other retinoids, such as all trans-retinoic acid, 13-cis retinoic acid and 9-cis retinoic acid, on 9 pancreatic cancer cell lines in relation to the effects on various cell cycle-regulating factors. After treatment with each retinoid, anti-proliferative effect was determined by the MTT method and expression of cell cycle-regulating factors, such as cyclins (D1, E and A), cyclin-dependent kinases (2 and 4), cyclin-dependent kinase inhibitors (p21 and p27) and retinoblastoma protein, was analyzed by Western blotting. Mofarotene showed half-maximal inhibition of cell proliferation at concentrations between 0.14 x 10(-6) and 3.8 x 10(-6) mol/l with little cytotoxicity. In contrast, the other retinoids did not inhibit the growth of all cell lines by over 50% compared to controls. A marked increase in the fraction of cells in G1 phase of the cell cycle was observed after mofarotene treatment; this was associated with marked up-regulation of p21/p27 and a shift of retinoblastoma protein into the hypophosphorylated form. In conclusion, mofarotene inhibits the growth of pancreatic cancer cells by inducing G1-phase cell cycle-inhibitory factors (p21, p27 and hypophosphorylated form of Rb protein) and is considered to be a useful agent for pancreatic cancer treatment.

Expression of cyclin-dependent kinase inhibitor p21 protein or p27 protein is a favorable prognosis factor for gastric carcinoma

Expression of cyclin-dependent kinase inhibitor p21 protein or p27 protein is a favorable prognosis factor for gastric carcinoma

Cyclin-dependent kinase-like proteins in pea nuclei: their presence and role in cell proliferation

Although many putative cdk (cyclin-dependent kinase) homologue genes have been identified in higher plants, their function and involvement in cell proliferation are still unclear. In this work we investigated the presence and distribution of cdk-like proteins in root tip meristem nuclei at different germination times (before, during, and after the onset of cell proliferation) and in nuclei of differentiated leaves. Nuclear cdk-like proteins were found in the root meristem throughout seed germination with a higher amount in actively proliferating cells, but were not detected in differentiated leaf. Characterization of the detected pea cdk-like proteins by immunoblotting led to the identification of two specific principal proteins of 33.2 and 34 kDa with the cdk conserved motif PSTAIRE. The p33.2 protein was also recognized by the anti-human p33cdk2 antibody, suggesting that the p33.2 and p34 proteins could be pea homologues of human p33cdk2 and p34cdk1, involved in the G1-S and G2-M transitions, respectively. Additional analysis of pea cdk protein localization has shown partial localization of these proteins at DNA replication sites during the G1 to S transition. These microscopical and biochemical data support the hypothesis that, in pea nuclei as in mammals, many PSTAIRE-cdks are present with different functions related to cell proliferation, one of which is probably involved in the control of the G1-S transition.

085 Coordinate expressions of cyclin-dependent kinase inhibitors and high sulfur protein in human hair follicles

085 Coordinate expressions of cyclin-dependent kinase inhibitors and high sulfur protein in human hair follicles