Linked Life Data

21297664

Source:http://linkedlifedata.com/resource/pubmed/id/21297664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2011-6-23
pubmed:abstractText
The major heat shock protein Hsp72 is expressed at elevated levels in many human cancers and its expression correlates with tumor progression. Here, we investigated the role of Hsp72 in Her2 oncogene-induced neoplastic transformation and tumorigenesis. Expression of Her2 in untransformed MCF10A mammary epithelial cells caused transformation, as judged by foci formation in culture and tumorigenesis in xenografts. However, expression of Her2 in Hsp72-depleted cells failed to induce transformation. The anti-tumorigenic effects of Hsp72 downregulation were associated with cellular senescence because of accumulation of p21 and depletion of survivin. Accordingly, either knockdown of p21 or expression of survivin reversed this senescence process. Further, we developed an animal model of Hsp72-dependent breast cancer associated with expression of Her2. Knockout (KO) of Hsp72 almost completely suppressed tumorigenesis in the MMTVneu breast cancer mouse model. In young Hsp72 KO mice, expression of Her2 instead of mammary tissue hyperplasia led to suppression of duct development and blocked alveolar budding. These effects were due to massive cell senescence in mammary tissue, which was associated with upregulation of p21 and downregulation of survivin. Therefore, Hsp72 has an essential role in Her2-induced tumorigenesis by regulating oncogene-induced senescence pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2836-45
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Heat shock protein Hsp72 plays an essential role in Her2-induced mammary tumorigenesis.
pubmed:affiliation
Department of Biochemistry, Boston University School of Medicine, MA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural