Association of early phase of colorectal carcinogenesis with STAT3 activation and its relevance in apoptosis regulation.

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody. Cells purified from CRC tissues exhibited greater STAT3/pSTAT3 reactivity than peripheral blood mononuclear cells (PBMC) from healthy individuals, which served as control. apoptotic index (AI) was comparatively low in tissue specimens with STAT3/pSTAT3 expression. CRC cells with a comparatively less number of apoptotic cells, expressed a minimum number of Caspase-3 positive cells (4.73%), in comparison to healthy-PBMC (12.63%). CRC cells with high STAT3/pSTAT3 staining had cells with greater percentage of Bcl2 reactivity (23.05%), but less positivity with Caspase3 antibody (2.05%). Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis. Bcl-2, Cyclin D1 and Caspase-3 control the activity of apoptosis regulator, STAT3.

Alteration of p73 in acute myelogenous leukemia.

The frequency of p73 mutation is low in hematologic malignancies as well as solid tumors. In the present study, we scanned for mutations in the exons 4, 5, 6, and 7 of p73, as well as methylation of the CpG island in the untranslated region of exon 1, in 100 de novo AML patients. Four patients showed mutation in exon 5 and one in exon 6, and none of the patients showed mutation in exons 4 and 7. None of the patients showed p73 gene methylation. The expression level of p73 mRNA was also examined in 40 AML samples using reverse transcriptase-polymerase chain reaction. Only six AML patients showed p73 mRNA expression, as analyzed by RT-PCR analysis. However, p73 over-expression in 30% of patients was demonstrated by immunocytochemistry and Western blot analysis. Further, mutation of p73 has been correlated with p73 mRNA and p73 protein status. The results show the presence of over-expressed p73 mRNA and protein in the samples with mutated p73 gene. Thus, it is presumed that mutation of p73 might lead to production of defective p73 protein and p73 mRNA, and this might have a role in the process of leukemogenesis of AML. This report is the first demonstrating the presence of mutations in p73 gene in acute myelogenous leukemia.