Local effects of EGF, α‐TGF, and EGF‐like growth factors on lobuloalveolar development of the mouse mammary gland in vivo

Vonderhaar, Barbara K.

doi:10.1002/jcp.1041320324

Cited by 143 publications

(55 citation statements)

References 17 publications

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“…Members of the EGF ligand and receptor families are interesting candidates for perturbed signalling in this tissue, given their prominent role in mammary branching and development (10,12,15,49,57), Sli-1's proposed role in attenuating EGF receptor signalling in C. elegans (64), and c-Cbl's interaction with the EGF receptor in murine cell lines (4,17).…”

Section: Discussionmentioning

confidence: 99%

Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice

Murphy

Schnall

Venter

et al. 1998

Molecular and Cellular Biology

349

335

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Section: Discussionmentioning

confidence: 99%

Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice

Murphy

Schnall

Venter

et al. 1998

Molecular and Cellular Biology

349

335

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“…EGF and amphiregulin are expressed in the ductal epithelial cells and TGFα is expressed in cap stem cells in the terminal end buds (Kenney et al, 1995;Snedeker et al, 1992). EGF and TGFα, bind to EGF receptor (ERB1) and can stimulate the proliferation of mammary epithelial cells and enhance lobular-aveolar development in the mammary gland of virgin mice (Vonderhaar, 1987). These growth factors can also prevent milk protein expression in HC11 cells and inhibit apoptosis of secretory alveolar epithelial cells in the involuting mammary gland .…”

Section: Discussionmentioning

confidence: 99%

Dominant negative Ras enhances lactogenic hormone‐induced differentiation by blocking activation of the Raf–Mek–Erk signal transduction pathway

Cerrito

Galbaugh

Wang

et al. 2004

Journal Cellular Physiology

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EGF and Ras mitogenic signal transduction pathways are frequently activated in breast carcinoma and inhibit mammary differentiation and apoptosis. HC11 mouse mammary epithelial cells, which differentiate and synthesize β-casein following growth to confluency and stimulation with lactogenic hormones, were used to study EGF-dependent signaling during differentiation. Blocking Mek-Erk or phosphotidylinositol-3-kinase (PI-3 kinase) signaling with specific chemical inhibitors enhanced β-casein promotor-driven luciferase activity. Because EGF stimulation of HC11 cells resulted in the activation of Ras, the effect of activated Ras (RasV12) or dominant negative (DNRasN17) on lactogen induced differentiation was examined. HC11 cell lines expressing RasV12 or DNRasN17 under the control of a tetracycline(tet)-responsive promotor were constructed. Activated RasV12 expression resulted in reduced tyrosine phosphorylation of Stat5 and a delay in β-casein expression in response to prolactin. However, the expression of tet-regulated DNRasN17 and adenovirusencoded DNRasN17 enhanced Stat5 tyrosine phosphorylation, Stat5 DNA binding and β-casein transcription. The expression of DNRasN17 blocked the activation of the Mek-Erk pathway by EGF but did not prevent the phosphorylation of AKT, a measure of activation of the PI-3-kinase pathway. Moreover, the expression of DNRasN17 prevented the block to lactogenic differentiation induced by EGF. Stimulation of HC11 cells with prolactin resulted in the association of the SHP2 phosphatase with Stat5, and this association was prevented by DNRasN17 expression. These results demonstrate that in HC11 cells DNRas inhibits the Mek-Erk pathway and enhances lactogenic hormone-induced differentiation. This occurs, in part, by inhibiting the association of the SHP2 phosphatase with Stat5.

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“…TGFa is structurally and functionally similar to EGF; the peptides share a 42% identity and can elicit the same biological eects in cultured mammary epithelial cells and explants (Daniel and Silberstein, 1985;Salomon et al, 1987;Vonderhaar, 1987). TGFa is often co-expressed with the EGFR and binding to the receptor activates the EGFRs' endogenous tyrosine kinase activity.…”

Section: Tgfa and Egfr Expression Coincides With Normal Proliferationmentioning

confidence: 99%

Transforming growth factor alpha and mouse models of human breast cancer

Humphreys

Hennighausen

2000

Oncogene

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Transforming growth factor alpha (TGFa) is a principal molecule in the normal and neoplastic development of the mammary gland. Binding of TGFa to the epidermal growth factor receptor (EGFR), activates the EGFRs' endogenous tyrosine kinase activity and stimulates growth of the epithelium in the virgin and pregnant mouse mammary gland. TGFa expression can be detected in breast cancer cells in vivo and in vitro and overexpression can elicit partial transformation or immortalized human and rodent mammary epithelial cells. Despite evidence implicating TGFa in the development of mammary neoplasia, the actual mechanism of TGFa-induced transformation is unclear. Transgenic mouse models targeting heterologus TGFa to the mammary gland have established TGFa overexpression can induce hyperproliferation, hyperplasia and occasional carcinoma. These transgenic studies demonstrated a facilitating, proliferative role for TGFa in the development of neoplasia and implicated several oncogenes that can cooperate with TGFa to transform the mammary epithelium. From studies of EGFR signaling pathways, inhibitory and modulating agents such as anti-EGFR antibodies and speci®c kinases inhibitors have been used to block the action of this pathway and prevent the development of TGFa-induced neoplasia and tumor formation. Studies in Stat5a knockout mice have established that the JAK2/Stat5a pathway can facilitate the survival of the mammary epithelium and can impact the progression of TGFa-mandated mammary tumorigenesis. Together these experiments indicate that TGFa and the EGFR signaling pathway are potentially amenable to therapies for treatment of human breast disease.

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Local effects of EGF, α‐TGF, and EGF‐like growth factors on lobuloalveolar development of the mouse mammary gland in vivo

Cited by 143 publications

References 17 publications

Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice

Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice

Dominant negative Ras enhances lactogenic hormone‐induced differentiation by blocking activation of the Raf–Mek–Erk signal transduction pathway

Transforming growth factor alpha and mouse models of human breast cancer

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