RbBP6 gene expression in cancers Free

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RbBP6 deficient cells have been found to be resistant to apoptosis induced by chemical inducers and this directly links RbBP6 to apoptosis. The RbBP6 gene is 36 kb long and contains 18 exons. It is transcribed to two mRNA transcripts, 1.1 kb and 6.1 kb and the latter is alternatively spliced in exon 16. The two mRNAs are transcribed to a 13 kD and a 200 kD proteins respectively. The 13 kD protein contains the DWNN domain only whereas the 200 kD proteins have the RING Finger, Rb and p53 binding domains linked to the DWNN domain. The aim of the study was to determine the expression pattern and tissue distribution of RbBP6 gene products in normal and diseased human tissues. We have studied several cancers compared the expression pattern and levels of expression to normal tissues. We have also compared the levels of expression and apoptosis in these tissues. Using both in situ hybridization and immunocytochemistry, we have found that in most if not all cancers, RbBP6, is found upregulated and in some cancers we found that it accumulates in the cytoplasm like the mutated p53. The nuclei in some instances did show some localization in some cancers as well. In normal tissues RbBP6 was found to be localizing mostly in nuclei and rarely in the cytoplasm. We have found that RbBP6 is upregulated around islands of tumors in well differentiated squamous tumors where the apoptosis is high and very much involved in fighting the invading tumors and there was none or little RbBP6 localization in the islands of tumors where apoptosis had completely halted. The RbBP6 expression level correlated with apoptosis and was found to be inversely proportional to proliferation as it was shown by TUNEL and Ki67 respectively. We have also used real time quantitative RT-PCR using Roche Light Cycler and have confirmed that the RbBP6 expression levels are increased in tumors as compared to normal respective tissues. The RbBP6 200 cDNA variant had previously been cloned by detecting its interaction with tumor suppressor proteins p53 and Rb, which have a major role in apoptosis and cancer development. Accumulation of these proteins, p53 and RbBP6, suggests that RbBP6 may be involved in a p53 dependant apoptotic pathway.