ErbB2 is required for ductal morphogenesis of the mammary gland

Jackson-Fisher, Amy; Bellinger, Gary; Ramabhadran, Rajani; Morris, Jacqueline K.; Lee, Kuo‐Fen; Stern, David F.

doi:10.1073/pnas.0407057101

Cited by 72 publications

(63 citation statements)

References 41 publications

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“…JARID1B was initially identified as a potential downstream target of HER2/ERBB2, which is also required for mammary ductal morphogenesis (48). This connection suggests that JARID1B may act downstream of HER2 in both mammary gland development and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Zou

Cao

Liu

et al. 2014

Journal of Biological Chemistry

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Background: Histone demethylase JARID1B is a potential oncoprotein, but its in vivo roles are not well understood. Results: Mice lacking JARID1B showed delayed mammary gland development and decreased female fertility. Conclusion: JARID1B promotes luminal lineage transcription programs in the mammary gland and fine-tunes systemic estrogen level. Significance: JARID1B functions in cancer are likely linked to its roles in gene regulation and mammary gland development.

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Section: Discussionmentioning

confidence: 99%

Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Zou

Cao

Liu

et al. 2014

Journal of Biological Chemistry

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“…The receptor tyrosine kinase gene ERBB2 or HER2/neu is amplified in 25% to 30% of all breast cancers and is associated with poor prognosis (45), whereas its role in the normal breast is linked to pregnancy and lactation in the mouse mammary gland (46). Recent evidence suggests that ERα and ErbB2 collaborate in mediating estrogen-induced mitogenesis, and therefore, the downregulation of ERBB2 in the parous group also may be linked to a protective effect (47).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Patterns in the Human Breast after Pregnancy

Asztalos

Gann

Hayes

et al. 2010

Cancer Prevention Research

118

117

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Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammationassociated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor α (ERα, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-β (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk. Cancer Prev Res; 3(3); 301-11. ©2010 AACR.

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“…Although this could reflect downregulation of epithelial ErbB2 signaling, the mammary-targeted expression of a dominant-negative ErbB2 transgene causes alveolar defects that only become apparent in dams at parturition [76]. Nevertheless, genetically rescued (cardiac ErbB2 transgenic) ErbB2-null mammary glands do exhibit delayed ductal penetration and TEB defects when they are transplanted to cleared wild-type mammary fat pads, though they do eventually catch up and undergo lactational differentiation [77]. In this instance, only epithelial ErbB2 is required, since the host fat pads contain ErbB2 (and EGFR).…”

Section: Does Egfr Affect Ductal Development Alone or In Concert Withmentioning

confidence: 99%

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

Sternlicht

Sunnarborg

2008

J Mammary Gland Biol Neoplasia

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In order to fulfill its function of producing and delivering sufficient milk to newborn mammalian offspring, the mammary gland first has to form an extensive ductal network. As in all phases of mammary development, hormonal cues elicit local intra-and inter-cellular signaling cascades that regulate ductal growth and differentiation. Among other things, ductal development requires the epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the transmembrane metalloproteinase AD-AM17, which can cleave and release AREG from the cell surface so that it may interact with its receptor. Tissue recombination and transplantation studies demonstrate that EGFR phosphorylation and ductal development proceed only when ADAM17 and AREG are expressed on mammary epithelial cells and EGFR is present on stromal cells, and that local administration of soluble AREG can rescue the development of ADAM17-deficient transplants. Thus proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stromal responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree. This, however, raises new issues concerning what may act upstream, downstream or in parallel with the ADAM17-AREG-EGFR axis, how it may become hijacked or corrupted during the onset and evolution of cancer, and how such ill effects may be confronted.

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ErbB2 is required for ductal morphogenesis of the mammary gland

Cited by 72 publications

References 41 publications

Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Gene Expression Patterns in the Human Breast after Pregnancy

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

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