ABSTRACT
Objective To evaluate the expression and the relativity of PMS2,Akt1 and P-AktS473 protein in A2780,Caov3,C13* and ES2 ovarian cancer cell lines .Methods The expression of PMS2 ,Akt1 and P-Akt S473 protein in A2780 ,Caov3 ,C13*and ES2 ovarian cancer cells was detected by Western Blot .After treated with IGF-1 (Akt1 activator) and API-2 (specific Akt1 in-hibitor) ,Caov3 ,ES2 and A2780 cells were collected and the level of PMS2 was detected by Western Blot .Results PMS2 ,Akt1 and P-Akt S473 proteins were detected in all of the four ovarian cancer cell lines with varied expression levels ,and the activity of Akt1 was inversely related to PMS2 expression in ovarian cancer cells .Exposed to Akt kinase stimulator IGF-1 ,ES2 and Caov3 cells were detected with a dramatically PMS2 decreasing .Meanwhile ,the decreasing of PMS2 protein was time-dependent on IGF-1 .Treated with API-2 ,Akt kinase specific inhibitor ,A2780 was detected with PMS2 dramatically increasing ,and the increasing of PMS2 pro-tein was time-dependent on API-2 .Conclusion In ovarian cancer cells ,PMS2 expression could be directly regulated by activated Akt1 .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate whether the functional polymorphisms in the promoter region of MMP-12 (-82A/G) and MMP-13(-77A/G) are associated with epithelial ovarian carcinoma (EOC).</p><p><b>METHODS</b>The MMP-12 -82A/G and MMP-13 -77A/G were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 300 epithelial ovarian carcinoma patients and 300 control women.</p><p><b>RESULTS</b>The A/G genotype frequency of the MMP-12 gene was significantly higher in the patients than in the controls (P= 0.003); similarly, the frequency of MMP-12 -82G allele was higher in the patient group (P= 0.004). Compared with the A/A genotype, the A/G genotype carriers significantly increased the risk of EOC development (OR= 2.81, 95%CI: 1.38-5.74). No overall association between the MMP-13 -77A/G polymorphism and EOC(P= 0.15) was observed. However, the A/A genotype carriers in the MMP-13 -77A/G locus had significantly higher risk of developing serous-papillary and mucinous ovarian cancer (OR= 1.93, 95% CI: 1.05-3.53; OR= 5.16, 95% CI: 1.62-16.44, respectively), comparing with the G/G genotype carriers. Combining the two SNPs, the haplotype distributions in patients were not significantly different from that in control women (P= 0.06).</p><p><b>CONCLUSION</b>These results suggested that individuals with MMP-12 -82A/G and MMP-13 -77A/A might have higher risk of overall or special histological type of EOC development.</p>