Cyclic AMP regulates formation of mammary epithelial acini in vitro
| العنوان: | Cyclic AMP regulates formation of mammary epithelial acini in vitro |
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| المؤلفون: | Pavel I. Nedvetsky, Jayanta Debnath, Sang Ho Kwon, Keith E. Mostov |
| المصدر: | Molecular Biology of the Cell Nedvetsky, PI; Kwon, SH; Debnath, J; & Mostov, KE. (2012). Cyclic AMP regulates formation of mammary epithelial acini in vitro. Molecular Biology of the Cell, 23(15), 2973-2981. doi: 10.1091/mbc.E12-02-0078. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3qk7v5r3Test |
| بيانات النشر: | The American Society for Cell Biology, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Programmed cell death, Morphogenesis, Cell Culture Techniques, Apoptosis, Acinar Cells, Biology, Integrin alpha6, Cell Line, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Acinus, medicine, Cyclic AMP, Humans, Protein kinase A, Mammary Glands, Human, Molecular Biology, 030304 developmental biology, 0303 health sciences, Cell Biology, Articles, Cyclic AMP-Dependent Protein Kinases, In vitro, Signaling, Cell biology, Extracellular Matrix, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Cell culture, 030220 oncology & carcinogenesis, Female |
| الوصف: | Cyclic AMP–dependent protein kinase A (PKA) is required for MCF10A mammary epithelial acinus formation in vitro. PKA plays a dual role by facilitating polarization of cells attached to the extracellular matrix and apoptosis of detached cells. Epithelial cells form tubular and acinar structures notable for a hollow lumen. In three-dimensional culture utilizing MCF10A mammary epithelial cells, acini form due to integrin-dependent polarization and survival of cells contacting extracellular matrix (ECM), and the apoptosis of inner cells of acini lacking contact with the ECM. In this paper, we report that cyclic AMP (cAMP)-dependent protein kinase A (PKA) promotes acinus formation via two mechanisms. First, cAMP accelerates redistribution of α6-integrin to the periphery of the acinus and thus facilitates the polarization of outer acinar cells. Blocking of α6-integrin function by inhibitory antibody prevents cAMP-dependent polarization. Second, cAMP promotes the death of inner cells occupying the lumen. In the absence of cAMP, apoptosis is delayed, resulting in perturbed luminal clearance. cAMP-dependent apoptosis is accompanied by a posttranscriptional PKA-dependent increase in the proapoptotic protein Bcl-2 interacting mediator of cell death. These data demonstrate that cAMP regulates lumen formation in mammary epithelial cells in vitro, both through acceleration of polarization of outer cells and apoptosis of inner cells of the acinus. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1939-4586 1059-1524 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65c72db0ce02a29ae94d8d75210be2efTest http://europepmc.org/articles/PMC3408423Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....65c72db0ce02a29ae94d8d75210be2ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 10591524 |
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