The breast proto-oncogene, HRGalpha regulates epithelial proliferation and lobuloalveolar development in the mouse mammary gland
Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1 isoform expressed in the mouse mammary gland and our previous experiments suggest that HRG1 has a unique role in mammary development. To determ...
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Published in | Oncogene Vol. 21; no. 32; pp. 4900 - 4907 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
25.07.2002
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Subjects | |
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Abstract | Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1 isoform expressed in the mouse mammary gland and our previous experiments suggest that HRG1 has a unique role in mammary development. To determine the function of HRGalpha activity during mouse mammary gland development, we generated a HRGalpha-deficient mouse strain. Unlike mice with HRG1 or isoform specific HRGbeta gene deletions, HRGalpha-null mice survive to adulthood. HRGalpha-deficient mice display pronounced defects in mammary gland lobuloalveolar development at 17 days of pregnancy and 3 days post-partum. Terminal and lateral ductal alveoli were condensed and alveolar outgrowth during pregnancy was severely impaired. A dramatic reduction in beta-casein expression accompanied defective alveolar development in the HRGalpha-null mice, as determined by in situ hybridization and Northern blot analysis of HRGalpha-deficient mammary glands at 3 days post-partum. Expression of the milk-protein genes WAP and alpha-lactalbumin was not adversely affected. In situ incorporation of BrdU demonstrated that epithelial proliferation was significantly curtailed in mammary glands of HRGalpha-deficient mice at 17 days post-coitus and 3 days post-partum. These results demonstrate that HRGalpha is an important mammary gland mitogen regulating alveolar development and lactogenesis. |
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AbstractList | Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1 isoform expressed in the mouse mammary gland and our previous experiments suggest that HRG1 has a unique role in mammary development. To determine the function of HRGalpha activity during mouse mammary gland development, we generated a HRGalpha-deficient mouse strain. Unlike mice with HRG1 or isoform specific HRGbeta gene deletions, HRGalpha-null mice survive to adulthood. HRGalpha-deficient mice display pronounced defects in mammary gland lobuloalveolar development at 17 days of pregnancy and 3 days post-partum. Terminal and lateral ductal alveoli were condensed and alveolar outgrowth during pregnancy was severely impaired. A dramatic reduction in beta-casein expression accompanied defective alveolar development in the HRGalpha-null mice, as determined by in situ hybridization and Northern blot analysis of HRGalpha-deficient mammary glands at 3 days post-partum. Expression of the milk-protein genes WAP and alpha-lactalbumin was not adversely affected. In situ incorporation of BrdU demonstrated that epithelial proliferation was significantly curtailed in mammary glands of HRGalpha-deficient mice at 17 days post-coitus and 3 days post-partum. These results demonstrate that HRGalpha is an important mammary gland mitogen regulating alveolar development and lactogenesis. |
Author | Birchmeier, Carmen Li, Li Long, Weiwen Jones, Frank E Cleary, Siobhan Mandarano, Michael A |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12118369$$D View this record in MEDLINE/PubMed |
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Snippet | Members of the EGF family of growth factors play critical roles during normal and neoplastic breast development. EGF family member HRGalpha is the only HRG1... |
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SubjectTerms | Animals Cell Division - genetics Epithelial Cells - cytology Epithelial Cells - physiology Female Gene Deletion Gene Expression Regulation, Developmental Mammary Glands, Animal - cytology Mammary Glands, Animal - embryology Mammary Glands, Animal - physiology Mice Morphogenesis - genetics Neuregulin-1 - deficiency Neuregulin-1 - genetics |
Title | The breast proto-oncogene, HRGalpha regulates epithelial proliferation and lobuloalveolar development in the mouse mammary gland |
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