Mechanisms of Marine Mammary Tumorigenesis Cooperation Between Tyrosine Kinase Receptors and Mutant p53

摘要

We are investigating cooperating genetic events in the genesis of breast cancer, using the mouse as a model system. We have shown cooperativity between a mutant allele of p53 and overexpressed ErbB2 in mammary tumorigenesis in transgenic mice. We are now performing a MMTV proviral mutagenesis screen to identify other events that can cooperate with these transgenes. We have put the mutant p53 allele onto the C3H background, and have generated mice that have both MMTV and mutant p53 transgene. These mice develop mammary tumor significantly faster than mice with MMTV alone (mice with mutant p53 alone do not develop tumors). These tumors are now being analyzed to identify the sites of proviral insertions. Other experiments, aimed at ErbB2 and MMTV were unsuccessful, but this may have been due to the mixed C3H x FVB strain background used in this cross.