Linked Life Data

17942928

Source:http://linkedlifedata.com/resource/pubmed/id/17942928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2007-10-18
pubmed:abstractText
The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A-positive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A-positive HCT 116 p53-/- variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9954-62
pubmed:meshHeading
pubmed-meshheading:17942928-Animals, pubmed-meshheading:17942928-Antigens, Neoplasm, pubmed-meshheading:17942928-Apoptosis, pubmed-meshheading:17942928-Cell Growth Processes, pubmed-meshheading:17942928-Cell Line, Tumor, pubmed-meshheading:17942928-DNA-Binding Proteins, pubmed-meshheading:17942928-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17942928-HCT116 Cells, pubmed-meshheading:17942928-Humans, pubmed-meshheading:17942928-Melanoma, pubmed-meshheading:17942928-Melanoma, Experimental, pubmed-meshheading:17942928-Mice, pubmed-meshheading:17942928-Mice, Inbred DBA, pubmed-meshheading:17942928-Nuclear Proteins, pubmed-meshheading:17942928-Protein Binding, pubmed-meshheading:17942928-Repressor Proteins, pubmed-meshheading:17942928-Transcription Factors, pubmed-meshheading:17942928-Tumor Suppressor Protein p53
pubmed:year
2007
pubmed:articleTitle
MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines.
pubmed:affiliation
Department of Dermatology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. byang@dermatology.wisc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural