EPITHELIAL PROLIFERATION AND DIFFERENTIATION IN THE MAMMARY-GLAND DO NOT CORRELATE WITH CFABP GENE-EXPRESSION DURING EARLY-PREGNANCY

Cardiac fatty acid binding protein (cFABP) is abundantly expressed in the nondividing, functionally differentiated mammary ephithelium. It i s very closely related, if not identical to, a previously described pr otein termed mammary derived growth inhibitor (MDGI). In vitro studies suggest that low concentrations of diffusible cFABP/MDGI may play a h ormone-like role in limiting proliferative activity and promoting func tional differentiation of this tissue, but no in vivo data to support this idea have been published. To test this hypothesis, we compared th e levels of cFABP mRNA with both the epithelial DNA labelling index an d levels of beta-casein mRNA in wild-type mice. We also investigated t he effect of a precocious experimental increase of cFABP levels in the mammary gland of transgenic mice on the labelling index and beta-case in mRNA levels. This was accomplished by expressing a bovine cFABP cDN A under the control of the ovine beta-lactoglobulin (BLG) gene promote r. We found that although both the DNA labelling index, beta-casein mR NA levels, and cFABP mRNA levels in wild-type mice are developmentally regulated, they do not correlate with each other during early pregnan cy in individual mice. Moreover, a three- to fourfold increase of tota l cFABP mRNA in two transgenic lines did not affect the DNA labelling index or the levels of beta-casein mRNA, an established marker of diff erentiation of the mammary epithelium, at this develop mental stage. T hese data suggest that epithelial DNA synthesis, beta-casein gene expr ession, and expression of the cFABP gene are regulated independently i n the proliferatively active mammary gland and that the rapidly dividi ng mammary epithelial cells are not susceptible to the action of cFABP during early pregnancy. (C) 1995 Wiley-Liss, Inc.