Source:http://linkedlifedata.com/resource/pubmed/id/15897890
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
32
|
| pubmed:dateCreated |
2005-7-28
|
| pubmed:databankReference | |
| pubmed:abstractText |
Loss of actin stress fibers has been associated with cell transformation and metastasis. TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes. Here, we investigated the mechanism underlying the failure of TGF-beta to induce stress fibers and inhibit cell migration in metastatic cells. RT-PCR analysis in carcinoma cell lines revealed a significant reduction in TPM1 transcripts in metastatic MDA-MB-231, MDA-MB-435 and SW620 cell lines. Treatment of these cells with demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) increased mRNA levels of TPM1 with no effect on TPM2. Importantly, 5-aza-dC treatment of MDA-MB-231 cells restored TGF-beta induction of TPM1 and formation of stress fibers. Forced expression of TPM1 by using Tet-Off system increased stress fibers in MDA-MB-231 cells and reduced cell migration. A potential CpG island spanning the TPM1 proximal promoter, exon 1, and the beginning of intron 1 was identified. Bisulfite sequencing showed significant cytosine methylation in metastatic cell lines that correlated with a reduced expression of TPM1. Together these results suggest that epigenetic suppression of TPM1 may alter TGF-beta tumor suppressor function and contribute to metastatic properties of tumor cells.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TPM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tropomyosin,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0950-9232
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
28
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
5043-52
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:15897890-Azacitidine,
pubmed-meshheading:15897890-Base Sequence,
pubmed-meshheading:15897890-Breast Neoplasms,
pubmed-meshheading:15897890-Cell Line, Tumor,
pubmed-meshheading:15897890-DNA Methylation,
pubmed-meshheading:15897890-Exons,
pubmed-meshheading:15897890-Female,
pubmed-meshheading:15897890-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15897890-Gene Silencing,
pubmed-meshheading:15897890-Genes, Tumor Suppressor,
pubmed-meshheading:15897890-Humans,
pubmed-meshheading:15897890-Introns,
pubmed-meshheading:15897890-Molecular Sequence Data,
pubmed-meshheading:15897890-Neoplasm Metastasis,
pubmed-meshheading:15897890-Promoter Regions, Genetic,
pubmed-meshheading:15897890-RNA, Messenger,
pubmed-meshheading:15897890-Transforming Growth Factor beta,
pubmed-meshheading:15897890-Tropomyosin
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Silencing of the Tropomyosin-1 gene by DNA methylation alters tumor suppressor function of TGF-beta.
|
| pubmed:affiliation |
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
|