Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-4-26
pubmed:abstractText
Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24-tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) tissues. Chromosomal analysis and DNA microarray were used to characterize these sublines. Real-time quantitative polymerase chain reaction and immunohistochemistry were used for validation. Epigenetic modifiers were used to study gene regulation. The cell viability was quantified with MTT assay. Chromosomal analysis revealed multiple alterations in metastatic cell lines compared to T24-P. DNA microarray analysis showed that taxol resistance-associated gene (TRAG) 3 was the most upregulated gene. From real-time quantitative polymerase chain reaction and immunohistochemistry, TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation but not histone acetylation. Interestingly, T24-B and T24-L cells were more resistant than T24-P to treatment with antimicrotubule agents such as docetaxel, paclitaxel and vinblastine. TRAG3 mRNA expression was higher in 20% of patients with ? pT2 (n = 10) and 60% of patients with ? pT3 (n = 20) compared to normal adjacent tissue (p = 0.05). In addition, the median TRAG3 expression was 6.7-fold higher in ? pT3 tumors compared to ? pT2 tumors. Knowing the status of TRAG3 expression could help clinicians tailor treatment to a particular patient population that could benefit from treatment, while allocating patients with resistant tumors to new experimental therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 UICC.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2823-32
pubmed:meshHeading
pubmed-meshheading:20734393-Adult, pubmed-meshheading:20734393-Aged, pubmed-meshheading:20734393-Aged, 80 and over, pubmed-meshheading:20734393-Animals, pubmed-meshheading:20734393-Base Sequence, pubmed-meshheading:20734393-Carcinoma, Transitional Cell, pubmed-meshheading:20734393-DNA Primers, pubmed-meshheading:20734393-Female, pubmed-meshheading:20734393-Humans, pubmed-meshheading:20734393-Male, pubmed-meshheading:20734393-Mice, pubmed-meshheading:20734393-Mice, Nude, pubmed-meshheading:20734393-Middle Aged, pubmed-meshheading:20734393-Neoplasm Metastasis, pubmed-meshheading:20734393-Neoplasm Proteins, pubmed-meshheading:20734393-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20734393-Polymerase Chain Reaction, pubmed-meshheading:20734393-Up-Regulation, pubmed-meshheading:20734393-Urinary Bladder Neoplasms
pubmed:year
2011
pubmed:articleTitle
Upregulation of TRAG3 gene in urothelial carcinoma of the bladder.
pubmed:affiliation
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural