Gene expression of chromosome in the rat Endometrial carcinoma

Abstract

The BDII rat is more likely to get hormone-dependent endometrial adenocarcinoma because of a gene. It was looked at to learn more about cancer in people. Comparative genome hybridization was used to look at tumors that grew on their own in BDII rats of mixed strains. Most problems were caused by a region on rat chromosome 4 called bands q12–q22 that was amplified. Tissue cultures from 11 endometrial carcinomas were used to check the copy number of 15 genes that are linked to cancer (10 endometrial adenocarcinomas and 1 endometrial squamous cell carcinomas).One person had pancreatic cancer and the other had peritoneal mesothelioma. In six of the tumors, the rat's chromosome 4 was made bigger. Met (hepatocyte growth factor receptor) and Cdk6 (cyclindependent kinase 6) were amplified the most and the most often. Five of the tumors had two amplified areas at 4q12-q13 and 4q21-q22, which were separated by an area that wasn't amplified at 4q13-q21. Through fluorescence in situ hybridization of tumor metaphases, it was found that the Cdk6 and Met sequences that were amplified were in areas that usually stained the same color (HSRs). In three of the tumors, both gene amplifications were found in the same HSRs. In the other two tumors, the same gene amplifications were found in different HSRs. Also, Cdk6 and Met amplifications were always linked to higher gene expression, which suggests that these genes may be the ones that the amplifications were trying to affect. Met and its ligand, the normally quiet hepatocyte growth factor gene (Hgf), were found to be working together in the sixth tumor. Met sequences were also repeated a lot in this tumor, but not Cdk6 sequences. This finding strongly suggests that the tumor has an autocrine signaling circuit. When looked at as a whole, our results suggest that endometrial cancers in the BDII rat may be caused by increased expression of Cdk6 and/or Met.