Comparative Roles of Overexpressed and Mutated H-ras and K-ras in MammaryCarcinogenesis

摘要

The objective of this study is to characterize cellular and molecular events ofchemically induced rat mammary carcinogenesis by asking why is selective activation of the Harvey ras gene, but not other similar members of the ras gene family, associated with this model. This study is divided into three main objectives. First, the ability of the activated and wild-type forms df Harvey ras and Kirsten ras gene products was evaluated. Both oncogenes produced rat mammary tumors (therefore, excluding the possibility that Kirsten ras was not tumorigenic in the rat mammary gland), although the Harvey ras gene product was more tumorigenic. Second, the relative mutation frequency of Harvey ras and Kirsten ras genes in nitromethylurea exposed rat mammary clonogenic growths are currently being determined. Third, a transgenic rat model has been developed to evaluate the role of Harvey ras gene regulation. Five founder animals expressing multiple copies of the Harvey ras gene have been produced. In one group, E transgene has been observed to reduce tumor multiplicity following carcinogen exposure. Three