Early Parity Significantly Elevates Mammary Tumor Incidence in MMTV-c-myc Transgenic Mice

Abstract

Female transgenic mice, in which a murine c-myc gene has been placed under the transcriptional control of the mouse mammary tumor virus long terminal repeat, are prone to developing mammary adenocarcinomas. Owing to the manner in which these mammary tumors develop, it is clear that exogenous expression of the c-myc transgene is necessary to but insufficient for murine mammary tumorigenesis. The genetic background of study mice has been shown to influence the phenotype induced by different transgenes; furthermore, mammary tumor initiation and progression induced by different transgenes has been shown to be susceptible to significant modification with alterations in and mixing of the genetic background of the study mice. We bred MMTV-c-myc transgenic mice onto a mixed genetic background that resulted in a very significant suppression of mammary tumor incidence for parous mice, bred continuously starting at 10 weeks of age. In this paper, we show that mammary tumor incidence is significantly elevated in these mixed background MMTV-c-myc transgenic mice when they are bred continuously, starting at 7 weeks of age. Early breeding of these mice did not influence mammary tumor multiplicity, latency, histopathology, or number of pregnancies at time of tumor development. These results are the first to demonstrate that breeding age influences mammary tumor incidence in MMTV-c-myc transgenic mice. They suggest that mammary gland susceptibility to tumorigenesis, resulting from the expression of c-myc, may vary with glandular development as is seen for chemical carcinogens.