Molecular biology of the proliferation of mammary epithelial cells

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A growth factor such as insulin, IGF-I or EGF is essential for the proliferation of mammary epithelial cells in cell culture systems. Prolactin and progesterone can stimulate cell growth only in the presence of one of these growth factors. These growth factors phosphorylate and activate MAP kinase in the process of their signal transduction. We have examined the presence of MAP kinase during the early pregnancy when the mammary epithelium proliferates, and lactation when its proliferation rate is low, by the immunoblotting. MAP kinase always exists, and will be ready to react to the signal. However, we are not yet successful to detect band shift corresponding to the phosphorylation state of the kinase. We also investigated the phosphorylation and activation of MAP kinase in synchronized Nb2 cells, which is specifically stimulated for growth by prolactin. No change in the enzyme activity was observed after prolactin stimulation. Some other passway of signal transduction may be used because the activation of nuclear oncogene c-myc is known in Nb2 cells. Mammary epithelial cells of any stage can differentiate finally and initiate secretion by a combination of insulin, glucocorticoid and prolactin. At the final differentiation, prolactin receptor is induces. This induction was demonstrated at the level of transcription by the competitive PCR method. The increase in mRNA is stimulated by glucocorticoid and inhibited by progesterone.