p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF.
p130Cas adaptor protein regulates basic processes such as cell cycle control, survival and migration. p130Cas over-expression has been related to mammary gland transformation, however the in vivo consequences of p130Cas over-expression during mammary gland morphogenesis are not known. In ex vivo mam...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3519769?pdf=render |
| _version_ | 1818061348549951488 |
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| author | Maria del Pilar Camacho Leal Alessandra Pincini Giusy Tornillo Elisa Fiorito Brigitte Bisaro Elisa Di Luca Emilia Turco Paola Defilippi Sara Cabodi |
| author_facet | Maria del Pilar Camacho Leal Alessandra Pincini Giusy Tornillo Elisa Fiorito Brigitte Bisaro Elisa Di Luca Emilia Turco Paola Defilippi Sara Cabodi |
| author_sort | Maria del Pilar Camacho Leal |
| collection | DOAJ |
| description | p130Cas adaptor protein regulates basic processes such as cell cycle control, survival and migration. p130Cas over-expression has been related to mammary gland transformation, however the in vivo consequences of p130Cas over-expression during mammary gland morphogenesis are not known. In ex vivo mammary explants from MMTV-p130Cas transgenic mice, we show that p130Cas impairs the functional interplay between Epidermal Growth Factor Receptor (EGFR) and Estrogen Receptor (ER) during mammary gland development. Indeed, we demonstrate that p130Cas over-expression upon the concomitant stimulation with EGF and estrogen (E2) severely impairs mammary morphogenesis giving rise to enlarged multicellular spherical structures with altered architecture and absence of the central lumen. These filled acinar structures are characterized by increased cell survival and proliferation and by a strong activation of Erk1/2 MAPKs and Akt. Interestingly, antagonizing the ER activity is sufficient to re-establish branching morphogenesis and normal Erk1/2 MAPK activity. Overall, these results indicate that high levels of p130Cas expression profoundly affect mammary morphogenesis by altering epithelial architecture, survival and unbalancing Erk1/2 MAPKs activation in response to growth factors and hormones. These results suggest that alteration of morphogenetic pathways due to p130Cas over-expression might prime mammary epithelium to tumorigenesis. |
| first_indexed | 2024-12-10T13:46:53Z |
| format | Article |
| id | doaj.art-24197419f6fb486ba33fe11095f216b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T13:46:53Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-24197419f6fb486ba33fe11095f216b02022-12-22T01:46:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e4981710.1371/journal.pone.0049817p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF.Maria del Pilar Camacho LealAlessandra PinciniGiusy TornilloElisa FioritoBrigitte BisaroElisa Di LucaEmilia TurcoPaola DefilippiSara Cabodip130Cas adaptor protein regulates basic processes such as cell cycle control, survival and migration. p130Cas over-expression has been related to mammary gland transformation, however the in vivo consequences of p130Cas over-expression during mammary gland morphogenesis are not known. In ex vivo mammary explants from MMTV-p130Cas transgenic mice, we show that p130Cas impairs the functional interplay between Epidermal Growth Factor Receptor (EGFR) and Estrogen Receptor (ER) during mammary gland development. Indeed, we demonstrate that p130Cas over-expression upon the concomitant stimulation with EGF and estrogen (E2) severely impairs mammary morphogenesis giving rise to enlarged multicellular spherical structures with altered architecture and absence of the central lumen. These filled acinar structures are characterized by increased cell survival and proliferation and by a strong activation of Erk1/2 MAPKs and Akt. Interestingly, antagonizing the ER activity is sufficient to re-establish branching morphogenesis and normal Erk1/2 MAPK activity. Overall, these results indicate that high levels of p130Cas expression profoundly affect mammary morphogenesis by altering epithelial architecture, survival and unbalancing Erk1/2 MAPKs activation in response to growth factors and hormones. These results suggest that alteration of morphogenetic pathways due to p130Cas over-expression might prime mammary epithelium to tumorigenesis.http://europepmc.org/articles/PMC3519769?pdf=render |
| spellingShingle | Maria del Pilar Camacho Leal Alessandra Pincini Giusy Tornillo Elisa Fiorito Brigitte Bisaro Elisa Di Luca Emilia Turco Paola Defilippi Sara Cabodi p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. PLoS ONE |
| title | p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. |
| title_full | p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. |
| title_fullStr | p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. |
| title_full_unstemmed | p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. |
| title_short | p130Cas over-expression impairs mammary branching morphogenesis in response to estrogen and EGF. |
| title_sort | p130cas over expression impairs mammary branching morphogenesis in response to estrogen and egf |
| url | http://europepmc.org/articles/PMC3519769?pdf=render |
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