Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development

Eleanor Y.M. Sum, Mark Shackleton, Kyungmin Hahm, Richard M. Thomas, Lorraine A. O'Reilly, Kay-Uwe Wagner, Geoffrey J. Lindeman, Jane E. Visvader

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

LMO4, a member of the LIM-only family of zinc-finger proteins, is overexpressed in a significant proportion of breast carcinomas and acts as a negative regulator of mammary epithelial differentiation. To delineate cell types within the developing mouse mammary gland that express Lmo4, we analysed different stages of mammopoiesis by immunohistochemistry. Lmo4 was found to be highly expressed in the proliferating cap cells of the terminal end bud and in the ductal and alveolar luminal cells of the mature mammary gland but was negligible or low in myoepithelial cells. To assess the physiological role of Lmo4 in the mammary gland, we generated conditionally targeted mice lacking Lmo4 in the mammary epithelium during pregnancy. Acute loss of Lmo4 in late pregnancy impaired lobuloalveolar development, accompanied by a two-fold reduction in the percentage of BrdU-positive cells. In contrast, germline loss of Lmo4 did not alter lobuloalveolar development arising from transplanted mammary anlagen, implying the existence of a compensatory mechanism in these knockout mice. Thus, the use of a conditional targeting strategy has revealed that Lmo4 is required for proper development of the mammary gland during pregnancy and indicated that Lmo4 acts as a positive regulator of alveolar epithelial proliferation.

Original languageEnglish (US)
Pages (from-to)4820-4828
Number of pages9
JournalOncogene
Volume24
Issue number30
DOIs
StatePublished - Jul 14 2005

Fingerprint

LIM Domain Proteins
Human Mammary Glands
Pregnancy
Breast
Alveolar Epithelial Cells
Zinc Fingers
Bromodeoxyuridine
Knockout Mice
Epithelium
Immunohistochemistry
Breast Neoplasms
Proteins

Keywords

  • Alveolar development
  • LIM domain
  • Mammary gland

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sum, E. Y. M., Shackleton, M., Hahm, K., Thomas, R. M., O'Reilly, L. A., Wagner, K-U., ... Visvader, J. E. (2005). Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Oncogene, 24(30), 4820-4828. https://doi.org/10.1038/sj.onc.1208638

Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. / Sum, Eleanor Y.M.; Shackleton, Mark; Hahm, Kyungmin; Thomas, Richard M.; O'Reilly, Lorraine A.; Wagner, Kay-Uwe; Lindeman, Geoffrey J.; Visvader, Jane E.

In: Oncogene, Vol. 24, No. 30, 14.07.2005, p. 4820-4828.

Research output: Contribution to journalArticle

Sum, EYM, Shackleton, M, Hahm, K, Thomas, RM, O'Reilly, LA, Wagner, K-U, Lindeman, GJ & Visvader, JE 2005, 'Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development', Oncogene, vol. 24, no. 30, pp. 4820-4828. https://doi.org/10.1038/sj.onc.1208638
Sum EYM, Shackleton M, Hahm K, Thomas RM, O'Reilly LA, Wagner K-U et al. Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Oncogene. 2005 Jul 14;24(30):4820-4828. https://doi.org/10.1038/sj.onc.1208638
Sum, Eleanor Y.M. ; Shackleton, Mark ; Hahm, Kyungmin ; Thomas, Richard M. ; O'Reilly, Lorraine A. ; Wagner, Kay-Uwe ; Lindeman, Geoffrey J. ; Visvader, Jane E. / Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. In: Oncogene. 2005 ; Vol. 24, No. 30. pp. 4820-4828.
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