Activated type I TGF beta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression
DC Field | Value | Language |
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dc.contributor.author | Muraoka-Cook, Rebecca S. | - |
dc.contributor.author | Shin, Incheol | - |
dc.contributor.author | Yin, Ji-Ye | - |
dc.contributor.author | Easterly, Emma G. | - |
dc.contributor.author | Barcellos-Hoff, Mary Helen | - |
dc.contributor.author | Yingling, J. M. | - |
dc.contributor.author | Zent, Roy | - |
dc.contributor.author | Arteaga, Carlos L. | - |
dc.date.accessioned | 2022-12-21T11:10:58Z | - |
dc.date.available | 2022-12-21T11:10:58Z | - |
dc.date.created | 2022-09-16 | - |
dc.date.issued | 2006-06 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181389 | - |
dc.description.abstract | We have examined the effects of transforming growth factor-beta (TGF beta) signaling on mammary epithelial cell survival. Transgenic mice expressing an active mutant of Alk5 in the mammary gland (MMTV-Alk5(T204D)) exhibited reduced apoptosis in terminal endbuds and during postlactational involution. Transgene-expressing mammary cells contained lower Smad2/3 and higher c-myc levels than controls, high ligand-independent phosphatidylinositol-3 kinase (PI3K) and Akt activities, and were insensitive to TGF beta-mediated growth arrest. Treatment with a proteasome inhibitor increased Smad2/3 levels and ligand-independent Smad transcriptional reporter activity, as well as reduced both c-myc protein and basal cell proliferation. Treatment with an Alk5 kinase small-molecule inhibitor upregulated Smad2/3 levels, reduced PI3K activity, P-Akt, and c-myc, and inhibited cell survival. Although Alk5(T204D)-expressing mice did not develop mammary tumors, bigenic MMTV-Alk(T204D) x Neu mice developed cancers that were more metastatic than those occurring in MMTV-Neu transgenics. These data suggest that (1) TGF beta can signal to PI3K/Akt and enhance mammary epithelial cell survival in vivo before cytological or histological evidence of transformation, and (2) TGF beta signaling can provide epithelial cells with a 'gain-of-function' effect that synergizes with oncogene-induced transformation. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Activated type I TGF beta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Shin, Incheol | - |
dc.identifier.doi | 10.1038/sj.onc.1208964 | - |
dc.identifier.scopusid | 2-s2.0-33745050200 | - |
dc.identifier.wosid | 000238448100006 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.25, no.24, pp.3408 - 3423 | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 25 | - |
dc.citation.number | 24 | - |
dc.citation.startPage | 3408 | - |
dc.citation.endPage | 3423 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE | - |
dc.subject.keywordPlus | SIGNAL-TRANSDUCTION | - |
dc.subject.keywordPlus | GLAND INVOLUTION | - |
dc.subject.keywordPlus | C-MYC | - |
dc.subject.keywordPlus | PHOSPHATIDYLINOSITOL 3-KINASE | - |
dc.subject.keywordPlus | MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | TGF-BETA-1 EXPRESSION | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordAuthor | TGF beta | - |
dc.subject.keywordAuthor | mammary cancer | - |
dc.subject.keywordAuthor | transgenic mice | - |
dc.subject.keywordAuthor | PI-3 kinase | - |
dc.subject.keywordAuthor | involution | - |
dc.subject.keywordAuthor | oncogenes | - |
dc.identifier.url | https://www.nature.com/articles/1208964 | - |
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