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

Leena Baker; Michael BeGora; Faith Au Yeung; Michael E. Feigin; Avi Z. Rosenberg; Scott W. Lowe; Kislinger Thomas Kislinger; Senthil K. Muthuswamy

doi:10.1242/jcs.185413

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

Leena Baker, Michael BeGora, Faith Au Yeung, Michael E. Feigin, Avi Z. Rosenberg, Scott W. Lowe, Kislinger Thomas Kislinger, Senthil K. Muthuswamy

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2307-2315
Number of pages	9
Journal	Journal of cell science
Volume	129
Issue number	12
DOIs	https://doi.org/10.1242/jcs.185413
State	Published - Jun 15 2016
Externally published	Yes

Keywords

Mammary alveologenesis
Proliferation
Scribble

ASJC Scopus subject areas

Cell Biology

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10.1242/jcs.185413

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title = "Scribble is required for pregnancy-induced alveologenesis in the adult mammary gland",

abstract = "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.",

keywords = "Mammary alveologenesis, Proliferation, Scribble",

author = "Leena Baker and Michael BeGora and Yeung, {Faith Au} and Feigin, {Michael E.} and Rosenberg, {Avi Z.} and Lowe, {Scott W.} and {Thomas Kislinger}, Kislinger and Muthuswamy, {Senthil K.}",

note = "Publisher Copyright: {\textcopyright} 2016.",

year = "2016",

month = jun,

day = "15",

doi = "10.1242/jcs.185413",

language = "English (US)",

volume = "129",

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AU - Baker, Leena

AU - BeGora, Michael

AU - Yeung, Faith Au

AU - Feigin, Michael E.

AU - Rosenberg, Avi Z.

AU - Lowe, Scott W.

AU - Thomas Kislinger, Kislinger

AU - Muthuswamy, Senthil K.

PY - 2016/6/15

Y1 - 2016/6/15

N2 - 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.

AB - 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.

KW - Mammary alveologenesis

KW - Proliferation

KW - Scribble

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AN - SCOPUS:84976496966

SN - 0021-9533

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JO - Journal of cell science

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IS - 12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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