Chakraborty S, Menon R, Banerjee M R
Int J Cancer. 1987 Jun 15;39(6):752-9. doi: 10.1002/ijc.2910390616.
The purpose of the present studies was to determine the influence of the chemopreventive agents selenium, 4-(hydroxyphenyl)-retinamide (4-HPR) and beta-carotene, on functional differentiation (lactogenesis) of the mouse mammary gland cells. The hormone-induced expression of the milk-protein genes, beta-casein, epsilon-casein and the whey acidic protein (WAP) was used as molecular marker of differentiation of the mammary cells in organ culture medium containing insulin, prolactin, aldosterone and hydrocortisone. Quantitative determination of the cellular concentration of the respective mRNA was ascertained by molecular hybridization of RNA to the specific cloned cDNA probes using both the solution and the filter hybridization methods. Selenium at 100 nm concentration caused a pronounced inhibition of accumulation of the respective mRNAs. The retinoid, 4-HPR, also caused a dose-dependent inhibition of expression of these mRNA sequences. In contrast, concentrations of the 3 mRNAs in beta-carotene-treated glands remained similar to those observed in glands cultured in medium containing the hormones and hexane (the latter being the solvent for beta-carotene). The significant antagonistic action of selenium and 4-HPR, however, was reversible after removal of the chemicals from the culture medium. Thus, among the 3 chemicals tested, selenium and retinoid can cause an adverse effect on functional differentiation (lactogenesis) of the mammary cells. This inhibitory effect, however, was reversible. beta-Carotene, on the other hand, caused no apparent antagonistic effect on expression of the milk-protein genes in the isolated whole mammary organ in culture.
本研究的目的是确定化学预防剂硒、4-（羟基苯基）视黄酰胺（4-HPR）和β-胡萝卜素对小鼠乳腺细胞功能分化（泌乳生成）的影响。在含有胰岛素、催乳素、醛固酮和氢化可的松的器官培养基中，激素诱导的乳蛋白基因β-酪蛋白、ε-酪蛋白和乳清酸性蛋白（WAP）的表达被用作乳腺细胞分化的分子标志物。通过使用溶液杂交和滤膜杂交方法，将RNA与特异性克隆的cDNA探针进行分子杂交，来定量测定各自mRNA的细胞浓度。100纳米浓度的硒导致各自mRNA的积累受到显著抑制。类视黄醇4-HPR也导致这些mRNA序列表达的剂量依赖性抑制。相比之下，β-胡萝卜素处理的腺体中这三种mRNA的浓度与在含有激素和己烷（后者是β-胡萝卜素的溶剂）的培养基中培养的腺体中观察到的浓度相似。然而，从培养基中去除化学物质后，硒和4-HPR的显著拮抗作用是可逆的。因此，在所测试的三种化学物质中，硒和类视黄醇可对乳腺细胞的功能分化（泌乳生成）产生不利影响。然而，这种抑制作用是可逆的。另一方面，β-胡萝卜素对培养的离体完整乳腺器官中乳蛋白基因的表达没有明显的拮抗作用。
