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Publication : Altered gene expression in spontaneous hepatocellular carcinomas from male B6C3F1 mice.

First Author  Romach EH Year  1997
Journal  Mol Carcinog Volume  19
Issue  1 Pages  31-8
PubMed ID  9180926 Mgi Jnum  J:41291
Mgi Id  MGI:893461 Doi  10.1002/(sici)1098-2744(199705)19:1<31::aid-mc5>3.0.co;2-q
Citation  Romach EH, et al. (1997) Altered gene expression in spontaneous hepatocellular carcinomas from male B6C3F1 mice. Mol Carcinog 19(1):31-8
abstractText  In this study, we analyzed spontaneous hepatocellular carcinomas (HCCs) from male B6C3F1 mice for alterations in the expression of the genes for c-myc, insulin-like growth factor II (IGF-II), cyclin D1, transforming growth factor-alpha (TGF-alpha), and the epidermal growth factor receptor (EGFR). These genes are all important in growth control in the rodent liver, and therefore, alterations in these genes or their products may result in unregulated growth. Northern blot analysis demonstrated an increase in expression of c-myc mRNA in five of 21 (24%) spontaneous HCCs compared with nontumor tissue. Tumors that had an increase in c-myc mRNA did not have an amplified c-myc gene. Of the HCCs analyzed, 18 of 29 (62%) showed reexpression of IGF-II RNA when compared with controls. Cyclin D1 mRNA was overexpressed in seven of 27 (26%) of the tumors analyzed relative to controls. Tumors with an increase in cyclin D1 mRNA also overexpressed the cyclin D1 protein. RNA encoding for the EGFR was decreased in 21 of 23 (91%) HCCs when compared with controls. None of the 29 liver tumors analyzed for alterations in expression of TGF-alpha mRNA differed from controls. Also, each individual tumor had a unique set of molecular alterations even when different tumors from the same animal were analyzed. These novel findings suggest that IGF-II, cyclin D1. c-myc, and EGFR are important mediators of carcinogenesis in spontaneous mouse liver tumor formation.
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