Frequent ectopic expression of a placenta-specific gene at high levels in BALB/c mouse mammary carcinomas

A placenta-specific gene, MIPP, is transcriptionally regulated in BALB/c mice by a solo long terminal repeat (LTR) of an intracisternal A-particle (IAP), an endogenous retrotransposon. Expression of IAPs, which is also promoted by LTR sequences, is a frequent aberration in many mouse mammary tumors of BALB/c mice. Given that these retroelements and the placental gene have a common promoter, we hypothesized that the tumors also express the gene. Northern blot analysis and RT-PCR revealed high expression of the placenta-specific gene in BALB/c mouse mammary preneoplasias and carcinomas of diverse etiologies, but not in normal mammary gland from virgin, pregnant and lactating mice. The preneoplasias and tumors expressed two transcripts, one of which is apparently unique to the mammary lesions. The other transcript is the same as one expressed in placenta that is not promoted by the IAP LTR. Despite the parallel expression of the placental gene and IAPs in the mammary tissues, RT-PCR showed that LTR sequences are absent from tumor-associated MIPP transcripts. Southern analysis revealed no gross mutations of the MIPP gene in mammary preneoplasias and tumors. The ectopic expression of the placenta-specific gene in BALB/c mouse mammary preneoplasias and carcinomas raises the possibility that it acts as an oncogene.