Linked Life Data

15556294

Source:http://linkedlifedata.com/resource/pubmed/id/15556294

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-11-23
pubmed:abstractText
In the search for novel genes involved in the taxol resistance phenotype, prior studies of gene expression in taxol-resistant cell lines and their paired drug-sensitive parental lines using high-density Affymetrix microarrays identified MGC4175 as an overexpressed transcript. In this report, we characterize MGC4175 and demonstrate that seven of eight taxol- and doxorubicin-resistant cell lines overexpressed MGC4175 as compared to their chemotherapy naive parent lines. Sequence analyses of MGC4175 cDNA and the predicted amino acid sequence did not show significant homology to any known sequence or protein domain, with an open reading frame of 356 bp that is predicted to encode a protein product of 118 amino acids. Both the MGC4175 and MDR1 genes are located at chromosome position 7q21. Southern blot analysis demonstrated that a single copy of MGC4175 is present in the human genome, and MGC4175 overexpression is not caused by genomic amplification or gene arrangement. Human MGC4175 fused to the carboxy terminus of enhanced green fluorescent protein (EGFP) and expressed in U-2OS cells localized the protein to the perinuclear region with further studies colocalizing this protein to the mitochondria. The Cancer Profiling Arrays and the Cancer Cell Line Profiling Array demonstrated that MGC4175 is broadly expressed in various tissues with no significant difference of MGC4175 expression between chemotherapy naive tumor cells and normal cells. However, MGC4175 is overexpressed 1.2- to 12.3-fold after 48 h of taxol induction and 0.65- to 6.5-fold after doxorubicin induction in various human cancer cell lines. In light of the overexpression of MGC4175 in association with taxol exposure, drug resistance, the coexpression of MDR1 and the mitochondrial localization of its protein, we propose to name this transcript MDR1 and Mitochondrial Taxol Resistance Associated Gene (MM-TRAG) and suggest that MM-TRAG may play a role in the development of taxol resistance in human cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
340
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15556294-Blotting, Northern, pubmed-meshheading:15556294-Cell Line, Tumor, pubmed-meshheading:15556294-Chromosomes, Human, Pair 7, pubmed-meshheading:15556294-Doxorubicin, pubmed-meshheading:15556294-Drug Resistance, Neoplasm, pubmed-meshheading:15556294-Female, pubmed-meshheading:15556294-Gene Expression Profiling, pubmed-meshheading:15556294-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15556294-Green Fluorescent Proteins, pubmed-meshheading:15556294-Humans, pubmed-meshheading:15556294-Male, pubmed-meshheading:15556294-Membrane Proteins, pubmed-meshheading:15556294-Microscopy, Fluorescence, pubmed-meshheading:15556294-Microscopy, Phase-Contrast, pubmed-meshheading:15556294-Mitochondrial Proteins, pubmed-meshheading:15556294-Neoplasms, pubmed-meshheading:15556294-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15556294-Paclitaxel, pubmed-meshheading:15556294-Phenotype, pubmed-meshheading:15556294-Recombinant Fusion Proteins, pubmed-meshheading:15556294-Transfection
pubmed:year
2004
pubmed:articleTitle
MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines.
pubmed:affiliation
Department of Hematology/Oncology, Massachusetts General Hospital, Jackson 1029, 70 Blossom Street, Boston, MA 02114, USA. zduan@partners.org
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.