Dietary effects on gene expression in mammary tumorigenesis

Abstract

Studies were undertaken to determine the effect a high fat diet has on the hormonally controlled transcription of the Mtv-1 locus in C3Hf mice. The expression of this locus is the initiating event in mammary tumor development in the C3Hf mouse. Mice were weaned at 21 days to either a high fat diet containing 23.5 percent corn oil or to a low fat diet containing 5 percent corn oil. Mice were sacrificed at first, second, and third parity, or when they had developed mammary tumors, and their mammary glands and mammary tumors were isolated. RNA was isolated from all mammary glands and breast tumors and analyzed. The high fat diet accelerated the transcription of the Mtv-1 locus. The transcripts of this locus, which are never seen in C3Hf mouse mammary glands until second parity, were present in first parity mammary glands of 6 out of 10 high fat diet C3Hf mice which were studied. The mammary glands of 15 first parity C3Hf mice which were on the low fat diet were analyzed and none contained the Mtv-1 specific transcripts. In addition, mammary tumor development was detected earlier (11 vs. 17.8 months) and after fewer litters (2.1 vs. 4.2) on the average in high fat diet C3Hf mice. One C3Hf mouse on the high fat diet developed a breast tumor at six months without going through pregnancy. These results indicate that a high fat diet of 23.5 percent corn oil can accelerate hormonally controlled gene expression specifically linked to mammary tumorigenesis. This work suggests that the mechanism by which mammary tumors develop earlier and after fewer litters in C3Hf mice on a high fat diet is the accelerated transcription of the hormonally controlled MMTV provirus present at the Mtv-1 locus.