PROLACTIN-MEDIATED GENE ACTIVATION IN MAMMARY EPITHELIAL CELLS

Mammary epithelial cells grow and develop with the onset of sexual mat urity. In addition, lobular alveolar structures are formed during preg nancy, and quiescent differentiated cells secrete high levels of milk proteins after parturition. These events are governed by multiple horm ones and growth factors and involve the sequential and synergistic act ion of functionally distinct signal transduction pathways. Milk protei n genes have been analyzed and composite response elements have been i dentified in the promoter sequences. Transcription factors, which rela y the hormonal signals, bind to these sequences. The factor that confe rs prolactin stimulation to milk protein gene transcription has recent ly been identified. MGF/Stat5 is a latent transcription factor that be comes activated by a tyrosine-specific protein kinase, Jak2, associate d with the prolactin receptor. Tyrosine phosphorylation converts the l atent factor into one with DNA-binding and transcriptional activation potential. The regulation of MGF/Stat5 in vitro and in vivo indicates that it is a central component of the lactogenic hormone signaling pat hway. Involvement of MGF/Stat5 in the signaling by other cytokines ind icates that the same factor might be involved in regulation of growth- promoting genes, primarily in hematopoietic cells.