Linked Life Data

21610252

Source:http://linkedlifedata.com/resource/pubmed/id/21610252

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
174
pubmed:dateCreated
2011-5-25
pubmed:abstractText
The stress-activated protein kinase (SAPK) p38 can induce apoptosis, and its inhibition facilitates mammary tumorigenesis. We found that during mammary acinar morphogenesis in MCF-10A cells grown in three-dimensional culture, detachment of luminal cells from the basement membrane stimulated mitogen-activated protein kinase (MAPK) kinases 3 and 6 (MKK3/6) and p38? signaling to promote anoikis. p38? signaling increased transcription of the death-promoting protein BimEL by phosphorylating the activating transcription factor 2 (ATF-2) and increasing c-Jun protein abundance, leading to cell death by anoikis and acinar lumen formation. Inhibition of p38? or ATF-2 caused luminal filling reminiscent of that observed in ductal carcinoma in situ (DCIS). The mammary glands of MKK3/6 knockout mice (MKK3(-/-)/MKK6(+/- )) showed accelerated branching morphogenesis relative to those of wild-type mice, as well as ductal lumen occlusion due to reduced anoikis. This phenotype was recapitulated by systemic pharmacological inhibition of p38? and ? (p38?/?) in wild-type mice. Moreover, the development of DCIS-like lesions showing marked ductal occlusion was accelerated in MMTV-Neu transgenic mice treated with inhibitors of p38? and p38?. We conclude that p38? is crucial for the development of hollow ducts during mammary gland development, a function that may be crucial to its ability to suppress breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1937-9145
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
ra34
pubmed:dateRevised
2011-11-9
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
p38? Signaling Induces Anoikis and Lumen Formation During Mammary Morphogenesis.
pubmed:affiliation
Department of Medicine, Tisch Cancer Institute at Mount Sinai, Mount Sinai School of Medicine, New York, USA.
pubmed:publicationType
Journal Article