Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation

Robin Kuns, Joseph L. Kissil, Irene F. Newsham, Tyler Jacks, David H. Gutmann, Lawrence (Larry) Sherman

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    4.1B is a member of the protein 4.1 superfamily of proteins that link transmembrane proteins to the actin cytoskeleton. The 4.1B gene localizes to chromosome 18p11.3, which undergoes loss of heterozygosity in mammary tumors. Here, we examine the expression of 4.1B in murine mammary epithelium and find that 4.1B is dramatically upregulated in mammary epithelial cells during pregnancy when there is extensive cell proliferation. In contrast, 4.1B is not expressed in virgin, lactating, or involuting mammary epithelium. To examine the consequence of 4.1B loss on mammary epithelial cell proliferation, we analysed mammary glands in 4.1B-null mice. 4.1B loss results in a significant increase in mammary epithelial cell proliferation during pregnancy, but has no effect on mammary epithelial cell proliferation, in virgin or involuting mice. Furthermore, we show that 4.1B inhibits the proliferation of mammary epithelial cell lines by inducing a G1 cell cycle arrest, characterized by decreased cyclin A expression and reduced Rb phosphorylation, and accompanied by reduced erbB2 phosphorylation. This cell cycle arrest does not involve alterations in the activities of MAPK, JNK, or Akt. Collectively, our findings demonstrate that 4.1B regulates mammary epithelial cell proliferation during pregnancy and suggest that its loss may influence mammary carcinoma pathogenesis in multiparous women.

    Original languageEnglish (US)
    Pages (from-to)6502-6515
    Number of pages14
    JournalOncogene
    Volume24
    Issue number43
    DOIs
    StatePublished - Sep 29 2005

    Fingerprint

    Breast
    Epithelial Cells
    Pregnancy
    Cell Proliferation
    Proteins
    Epithelium
    Phosphorylation
    Breast Neoplasms
    G1 Phase Cell Cycle Checkpoints
    Cyclin A
    Loss of Heterozygosity
    Human Mammary Glands
    Cell Cycle Checkpoints
    Actin Cytoskeleton
    Chromosomes
    Cell Line
    Genes

    Keywords

    • erbB2
    • Mammary carcinoma
    • Mammary epithelial cells
    • Pregnancy
    • Protein 4.1B

    ASJC Scopus subject areas

    • Molecular Biology
    • Cancer Research
    • Genetics

    Cite this

    Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation. / Kuns, Robin; Kissil, Joseph L.; Newsham, Irene F.; Jacks, Tyler; Gutmann, David H.; Sherman, Lawrence (Larry).

    In: Oncogene, Vol. 24, No. 43, 29.09.2005, p. 6502-6515.

    Research output: Contribution to journalArticle

    Kuns, Robin ; Kissil, Joseph L. ; Newsham, Irene F. ; Jacks, Tyler ; Gutmann, David H. ; Sherman, Lawrence (Larry). / Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation. In: Oncogene. 2005 ; Vol. 24, No. 43. pp. 6502-6515.
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