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p21WAF1 Expression (p21waf1 + expression)
Selected AbstractsHeme oxygenase-1/p21WAF1 mediates peroxisome proliferator-activated receptor-, signaling inhibition of proliferation of rat pulmonary artery smooth muscle cellsFEBS JOURNAL, Issue 6 2010Manxiang Li Activation of peroxisome proliferator-activated receptor (PPAR)-, suppresses proliferation of rat pulmonary artery smooth muscle cells (PASMCs), and therefore ameliorates the development of pulmonary hypertension in animal models. However, the molecular mechanisms underlying this effect remain largely unknown. This study addressed this issue. The PPAR, agonist rosiglitazone dose-dependently stimulated heme oxygenase (HO)-1 expression in PASMCs, 5 ,m rosiglitazone inducing a 12.1-fold increase in the HO-1 protein level. Cells pre-exposed to rosiglitazone showed a dose-dependent reduction in proliferation in response to serotonin; this was abolished by pretransfection of cells with sequence-specific small interfering RNA against HO-1. In addition, rosiglitazone stimulated p21WAF1 expression in PASMCs, a 2.34-fold increase in the p21WAF1 protein level being achieved with 5 ,m rosiglitazone; again, this effect was blocked by knockdown of HO-1. Like loss of HO-1, loss of p21WAF1 through siRNA transfection also reversed the inhibitory effect of rosiglitazone on PASMC proliferation triggered by serotonin. Taken together, our findings suggest that activation of PPAR, induces HO-1 expression, and that this in turn stimulates p21WAF1 expression to suppress PASMC proliferation. Our study also indicates that rosiglitazone, a medicine widely used in the treatment of type 2 diabetes mellitus, has potential benefits for patients with pulmonary hypertension. [source] Epigenetics are involved in the regulation of the cell cycle and expression of tumor suppressor genes in human colon cancer cellsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2003Ying Xuan CHEN OBJECTIVE: To investigate the effects of DNA methylation and histone acetylation on the cell cycle progression and expression of tumor suppressor genes in human colon cancer (HCC) cell lines. METHODS: Three HCC cell lines (HT-29, SW1116 and Colo-320) were treated with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC) or/and histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) or sodium butyrate. The methylation status of the promoter of the p16INK4A gene was assayed by methylation-specific PCR (MSP). The expression of p16INK4A and p21WAF1 was analyzed by RT-PCR. The cell cycle distribution was determined by flow cytometry. RESULTS: Before treatment, p16INK4A expression was slightly detected in the three cell lines (HT-29, SW1116 and Colo-320) and p21WAF1 expression was not detected in SW1116 and Colo-320 cells. The methylation level of the p16INK4A gene promoter significantly decreased and mRNA expression markedly increased in HT-29 cells after treatment with 1 µmol/L, but not 10 µmol/L, of 5-aza-dC for 24 h. In the SW1116 and Colo-320 cells, the expression of p16INK4A was markedly enhanced at 10 µmol/L or 5 µmol/L of 5-aza-dC for 24 h. However, p21WAF1 gene expression was not detected. Interestingly, after treatment with TSA or sodium butyrate, the transcription of p21WAF1 was significantly upregulated in these two cell lines. Furthermore, 5-aza-dC did not affect cell cycle distribution, but TSA or sodium butyrate blocked the cell cycle, mainly in the G1 phase. CONCLUSIONS: The expression of the p16INK4A gene is regulated by DNA methylation in three HCC cell lines. The expression of p21WAF1 gene is regulated by histone acetylation in SW1116 and Colo-320. In these two cell lines, histone hyperacetylation causes a G1 cell cycle arrest. [source] Enhanced sensitivity to cis -diamminedichloro-platinum(II) of a human carcinoma cell line with mutated p53 gene by cyclin-dependent kinase inhibitor p21WAF1 expressionCANCER SCIENCE, Issue 3 2003Mamoru Satou p53-mediated induction of p21WAF1, a cyclin-dependent protein kinase inhibitor, is known to protect cancer cells from the cytotoxic effects of anti-cancer drugs or ,-irradiation. Since the p53 gene is frequently inactivated in cancer cells, we examined whether p21WAF1 expression may alter the sensitivity of cancer cells with mutated p53 gene to anti-cancer drugs. Cells of a colon cancer cell line DLD-1 were transfected with p21WAF1 expression vector controlled by a tetracycline-repressable promoter and transfec-tants were cloned (Dp21,1). p21WAF1 expression induced by removal of tetracycline from culture media repressed cell proliferation and resulted in altered cell shape, suggesting induction of differentiation. Dp21,1 cells with p21WAF1 expression were more sensitive to cis -diamminedichloroplatinum(II) (CDDP) (IC50 value, 10 ,M) than those without p21WAF1 expression (IC50, 22 ,M). Sensitivity to doxorubicin was not different between Dp21,1 cells with and without p21WAF1 expression. DNA ladder formation was observed in Dp21,1 cells treated with CDDP, indicating that the enhanced sensitivity to CDDP involves apoptosis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosolic protein revealed that subunit protein bands with Mr 55 kDa and 44 kDa were markedly increased in cells with p21WAF1 expression. By im-munoblotting, these proteins were identified as c-Jun N-terminal kinase (JNK) 2 and p38 mitogen-activated protein kinase (MAPK) 8, respectively, both of which are believed to be involved in apoptosis induction by CDDP. These results suggest that p21WAF1 may enhance the sensitivity of colon cancer cells with mutated p53 gene to CDDP, possibly through the JNK and p38 MAPK pathways. (Cancer Sci 2003; 94: 286,291) [source] | ||||||||||