Linked Life Data

16466399

Source:http://linkedlifedata.com/resource/pubmed/id/16466399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-2-9
pubmed:abstractText
To determine the role of transforming growth factor-beta (TGF-beta) signaling in mammary development and tumor formation, we previously generated transgenic mice that expressed a dominant-negative form of the TGF-beta type II receptor (DNIIR) under the control of DNA regulatory elements from the metallothionein promoter (MT-DNIIR-28). In this report, we tested the hypothesis that loss of TGF-beta signaling in the mammary gland alters the development of chemically or hormonally induced tumors in mice. Four groups of mice were used in the study: wild-type and MT-DNIIR-28 mice on zinc with pituitary isograft, and wild-type and MT-DNIIR-28 mice on zinc with pituitary isograft treated with the carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). Tumor-free survival over time, tumor growth rate, and tumor pathology were measured. Statistically significant differences in tumor free survival over time or tumor growth rate were not detected in wild-type versus transgenic mice treated with DMBA. In contrast, tumor-free survival was significantly altered in transgenic mice that were treated with the pituitary isograft alone with MT-DNIIR mice developing tumors more quickly. Alterations in the types of tumors that formed in wild-type versus MT-DNIIR DMBA-treated mice were detected. In wild-type mice, tumors with squamous differentiation or bicellular adenomyoepitheliomas were most common. Adenomyoepitheliomas were not detected in transgenic mice. Furthermore, there was reduced staining for alpha smooth muscle actin and keratin 14, markers for myoepithelial cells, in the glandular portion of tumors in transgenic mice. The pathology of tumors induced by pituitary isograft alone was also markedly different in wild-type and transgenic mice. All the tumors classified from wild-type mice demonstrated some form of squamous differentiation, whereas squamous differentiation was not detected in the pituitary-induced transgenic tumors. The results suggest that TGF-beta acts as a tumor suppressor for hormone-induced cancers and that TGF-beta has a role in determining tumor pathology by regulating myoepithelial or squamous differentiation, maintenance, or transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0301-4681
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40-52
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Transforming growth factor-beta signaling helps specify tumor type in DMBA and hormone-induced mammary cancers.
pubmed:affiliation
Department of Cell Biology, University of Alabama at Birmingham 1918 University Blvd, 310 MCLM Birmingham, AL 35294-0005, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural