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HORMONE INDUCIBLE MILK PROTEIN GENE EXPRESSION AND ITS RELEVANCE TO MAMMARY CARCINOGENESIS (ORGAN CULTURE, CHEMOPREVENTIVE AGENTS, CLONING)
Abstract
Selenium, 4-HPR and (beta)-carotene have a preventive influence during the transformation of mouse mammary epithelial cells induced by a variety of oncogenic chemicals. However, nothing is known about the effect of these agents on normal functional differentiation. Therefore, studies were done to determine the influence of the various chemopreventive agents on the hormone-inducible expression of the milk protein genes (beta)-casein, (epsilon)-casein and whey acidic protein, used as markers of differentiation. Mammary glands were cultured in medium containing insulin, prolactin, aldosterone, hydrocortisone and one of the chemopreventive agents. Quantitative determination of the cellular concentration of the respective mRNA was ascertained by molecular hybridization of RNA to the specific cloned cDNA probes. cDNA probes used for solution hybridization studies was prepared from cDNA clones in M13mp8 bacteriophage. cDNA copies of the insert DNA were synthesized with DNA polymerase I, primed with a sequencing primer. Selenium and 4-HPR caused a reversible, dose-dependent inhibition of the accumulation of these mRNA sequences, suggestive of an adverse effect of these compounds on functional differentiation. In contrast, concentrations of the three mRNAs in (beta)-carotene treated glands remained similar to that of the control glands. Prolactin, a polypeptide hormone, is essential for the growth and differentiation of the mouse mammary gland. Prolactin is also involved in osmoregulation in the mammary gland, a process activated by the cell membrane bound Na('+)/K('+) ATPase. However, no information is available on the intercellular factors that are responsible for the modulation of these functions of prolactin. An attempt was made to obtain clues to the understanding of this mechanism. Ouabain, an inhibitor of Na('+)/K('+) ATPase was used in the culture medium and the resulting effect of the compound on prolactin action was observed by measuring the level of expression of the milk protein genes. Results of filter hybridization and nuclear transcription experiments show that at 5 (mu)M concentration of ouabain, both accumulation and transcription of the milk protein genes are inhibited. This suggests a possible modulation of the action of prolactin by the monovalent cations.
Subject Area
Biology
Recommended Citation
CHAKRABORTY, SARBANI M, "HORMONE INDUCIBLE MILK PROTEIN GENE EXPRESSION AND ITS RELEVANCE TO MAMMARY CARCINOGENESIS (ORGAN CULTURE, CHEMOPREVENTIVE AGENTS, CLONING)" (1986). ETD collection for University of Nebraska-Lincoln. AAI8706223.
https://digitalcommons.unl.edu/dissertations/AAI8706223