The cell polarity protein scribble (SCRIB) is a crucial regulator of polarization, cell migration and tumorigenesis. 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 RNA interference (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 prolactin receptor (PRLR) at cell surface and its accumulation in intracellular structures that express markers of the Golgi complex 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.
The authors declare no competing or financial interests.
S.K.M. and L.B. conceived the study; L.B. performed the majority of the experiments and co-wrote the manuscript with S.K.M. M.B. performed Golgi localization studies. F.A. and T.K. assisted with surface protein analysis. M.F. and A.Z. we involved in generation of the inducible RNAi mice and S.L. shared his then unpublished technology to generate inducible RNAi mice.
This work was supported by the National Cancer Institute [grant number R01 CA098830]; an Era of Hope Scholar award from U.S. Department of Defense (DOD) Breast Cancer Research Program [grant number BC075024]; the Rita Allen Foundation; and the Lee K. Margaret Lau Chair for Breast Cancer Research; and Princess Margaret Cancer Foundation (to S.K.M.). This work was also funded in part by the Ontario Ministry of Health and Long-Term Care (OMOHLTC). The views expressed do not necessarily reflect those of the OMOHLTC. Deposited in PMC for release after 12 months.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.185413.supplemental
- Received December 31, 2015.
- Accepted April 30, 2016.
- © 2016. Published by The Company of Biologists Ltd