Molecular cloning of Copenhagen rat Krev-1 and rap1B cDNAs and study of their association with mammary tumor resistance in the Copenhagen rat.

The Copenhagen (Cop) rat is resistant to both spontaneous and induced mammary carcinogenesis. Here we examine the hypothesis that the putative suppressor gene Krev-1 (rap1A) or its related gene rap1B might be involved in this strain-specific resistance. We found equal expression of these two genes in mammary tissue from both resistant and susceptible rat strains. Since these genes can potentially be activated by several point mutations, the cDNAs from Cop Krev-1 (rap1A) and rap1B were cloned and sequenced. Only a one base difference in the Krev-1 sequences between the mammary tumor-susceptible Sprague-Dawley rat and the resistant Cop rat was found. This difference did not predict an altered amino acid sequence. The nucleotide sequence of rat rap1B had a 90% homology with its human counterpart and its deduced amino acid sequence was identical to the human sequence with the exception of amino acid 139. We thus conclude that it is unlikely that the Krev-1 or rap1B putative suppressor genes are involved in the mammary tumor-resistant phenotype of the Cop rat.