Methylation and expression of rat kappa-casein gene in normal and neoplastic rat mammary gland.
The kappa-casein mRNA was evaluated in the rat mammary gland during functional differentiation and neoplastic growth. Using a dot-blot assay, the mRNA was barely detectable in the virgin gland; it steadily increased from the onset of gestation and leveled off during lactation. In rat mammary tumors, either primary (7,12-dimethylbenz(a)anthracene-induced) or transplanted (MTW9), the level of kappa-casein mRNA was about 2.5-fold lower than in the lactating gland, but an extensive variation among individual tumors was observed. There was no detectable kappa-casein mRNA in rat liver. In the mammary gland of virgin, 10-day pregnant, and nonlactating females, the DNA sequences within and/or around the kappa-casein gene were found to be hypermethylated at the HpaII-MspI sites as compared to 10-day lactating females. In the two tumors studied, the kappa-casein gene was partially methylated at the same sites. Prolactin treatment induced kappa-casein gene expression in the virgin rat mammary gland but did not result in a change of the methylation status at the HpaII-MspI sites. Under similar conditions of prolactin treatment, however, the methylation of the Sau96I sites was reduced, and an inverse correlation between the onset of kappa-casein gene methylation and kappa-casein gene expression was evident in both the virgin gland and the tumors. Thus, the expression of kappa-casein was found to be inversely correlated with the extent of methylation of the kappa-casein gene, except in the case of the prolactin-stimulated virgin gland.
D000818:Animals; D001483:Base Sequence; D002364:Caseins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008745:Methylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D002364:Caseins; D004273:DNA, Neoplasm; D012333:RNA, Messenger