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The cell polarity protein SCRIB is a critical regulator of polarization, cell migration and tumourigenesis. Whereas SCRIB is known to regulate early stages of mouse mammary gland development, its function in the adult gland is not known. Using an inducible RNAi mouse model for downregulating SCRIB expression, we report an unexpected role for SCRIB as a positive regulator of cell proliferation during pregnancy associated mammary alveologenesis. SCRIB was required in the epithelial cell compartment of the mammary gland. Lack of SCRIB attenuated prolactin-induced activation of the JAK2/STAT5 signaling pathway. In addition, loss of SCRIB resulted in the downregulation of PRLR at cell surface and accumulation in intracellular structures that express markers of the Golgi apparatus and the recycling endosome. Unlike its role in virgin gland as a negative regulator cell proliferation, SCRIB is a positive regulator of mammary epithelial cell proliferation during pregnancy.

Scribble is required for pregnancy-induced alveologenesis in the adult mammary gland