In addition to Bmi-1, mammalian cells also express a Bmi-1-related PcG protein Mel-18.
The Mel-18 gene product is structurally highly similar to Bmi-1 protein. Interestingly, we have found that Bmi-1 is negatively regulated by Mel-18 and expression of Mel-18 negatively correlates with Bmi-1 in breast tumors, and Mel-18 overexpression in breast cancer cell line MCF7 results in downregulation of Bmi-1 and reduction of transformed phenotype [38]. Negative correlation between Bmi-1 and Mel-18 expression was also recently reported in hematopoietic stem cells [39]. Lee et al. also recently reported that overexpression of Mel-18 inhibits growth of breast cancer cells [40]. These data suggested that Mel-18 acts as a potential
selleck products tumor suppressor. However, the function of Mel-18 is still debatable. In few other studies, it was found that similar to Bmi-1, Mel-18 can act as an oncogene [41, 42]. So, the role of Mel-18 in cancers other than breast cancers and different pathological conditions is still not clear and need to be clarified. Gastric cancer is one of the most common malignancies throughout the world. It has been reported that Bmi-1 is overexpressed in gastric cancer and is an independent prognosis factor [32]. We have also studied the expression of Mel-18 and Bmi-1 in gastric tumors by immunohistochemistry (IHC). We found that eFT508 concentration gastric tumor tissues expressed significantly higher Bmi-1 and lower Mel-18, and the expression of Mel-18 negatively correlated with Bmi-1; there
was a significant positive correlation between Bmi-1 expression with lymph node metastasis, or LEE011 clinical stage, but there was no obvious correlation between Mel-18 expression and clinicopathological factors; downregulation of Bmi-1 by Mel-18 overexpression or knockdown of Bmi-1 expression was accompanied by decreased transformed phenotype and migration ability in gastric cancer cell lines in in vitro study[33]. So, the results of Bmi-1 expression correlated with L-gulonolactone oxidase lymph node metastasis or clinical stage in in vivo study was accordance with the results in in vitro study, while the results of no correlation was found between Mel-18 expression and clinicopathological factors in in vivo study was not accordance with the results in in vitro study, we suspected that one of the reason may due to the reliability of IHC method which was used to detect the expression of Bmi-1 and Mel-18 in tumor tissues in most paper of literature including our previous study. This method lacks standard procedure and evaluation criterion and its’ reliability depends on the specific of antibody. The results of quantitative Real time RT-PCR (QRT-PCR) with specific primer is more reliable than that of IHC to measure the gene expression level especially for Mel-18, which lacks specific mouse monoclonal antibody till now.