Ambili M, Jayasree K, Sudhakaran P R
Department of Biochemistry, University of Kerala, Kariavattom, Trivandrum 695581, India.
Biochim Biophys Acta. 1998 Jul 24;1403(3):219-31. doi: 10.1016/s0167-4889(98)00030-5.
Cell matrix interactions are critical in the expression and maintenance of differentiated functions in mammary gland. Matrix metalloproteinases (MMPs), by acting on different matrix components, contribute to the remodelling of extracellular matrix. Of the three major gelatinases found in rat mammary gland at different stages of ontogeny, 60K gelatinase, a Ca2+ dependent neutral MMP, seems to be involved in involution, as it appears at the late stage of involution. Further investigations on its regulation by hormones which influence the mammary gland function were carried out. Administration of beta-oestradiol caused the appearance of 60K gelatinase on the 2nd day of involution, while in untreated controls this activity was absent. On treatment of mammary epithelial cells of the 2nd day involuting tissue in culture with beta-oestradiol, the 60K gelatinase activity appeared, while the untreated controls did not show the activity. The effect of beta-oestradiol was studied further by metabolic labelling of the epithelial cells from the 2nd day involuting tissue. A concentration dependent increase in the amount of radiolabelled 60K gelatinase was found on treatment with beta-oestradiol. The upregulation of the 60K gelatinase activity in vivo was also found by immunocytochemical staining of the beta-oestradiol treated tissues. The effect of beta-oestradiol appears to be specific for 60K as the activity of other gelatinases (130K and 68K) in the mammary gland were not affected. Furthermore, a drastic regression of the mammary gland as evidenced by histochemical analysis and a marked decrease in the milk protein production in beta-oestradiol treated tissues indicated the onset of early involution. These results indicate that the 60K gelatinase which is upregulated during involution or on induction of early involution may play a key role in remodelling of extracellular matrix in mammary gland and further that this enzyme is subject to modulation by beta-oestradiol.
细胞与基质的相互作用对于乳腺中分化功能的表达和维持至关重要。基质金属蛋白酶（MMPs）通过作用于不同的基质成分，有助于细胞外基质的重塑。在大鼠乳腺发育的不同阶段发现的三种主要明胶酶中，60K明胶酶是一种依赖Ca2+的中性MMP，似乎参与了退化过程，因为它出现在退化后期。对其受影响乳腺功能的激素调节进行了进一步研究。给予β-雌二醇导致在退化第2天出现60K明胶酶，而未处理的对照组则没有这种活性。用β-雌二醇处理培养的第2天退化组织的乳腺上皮细胞时，出现了60K明胶酶活性，而未处理的对照组未显示该活性。通过对第2天退化组织的上皮细胞进行代谢标记，进一步研究了β-雌二醇的作用。在用β-雌二醇处理后，发现放射性标记的60K明胶酶量呈浓度依赖性增加。通过对β-雌二醇处理组织的免疫细胞化学染色，也发现了体内60K明胶酶活性的上调。β-雌二醇的作用似乎对60K是特异性的，因为乳腺中其他明胶酶（130K和68K）的活性未受影响。此外，组织化学分析表明乳腺明显退化，β-雌二醇处理组织中的乳蛋白产量显著下降，表明早期退化开始。这些结果表明，在退化过程中或早期退化诱导时上调的60K明胶酶可能在乳腺细胞外基质的重塑中起关键作用，并且该酶受β-雌二醇的调节。
