Differences in transcript levels of ABC transporters between pancreatic adenocarcinoma and nonneoplastic tissues
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- ATP-Binding Cassette Transporters genetics MeSH
- Drug Resistance, Neoplasm genetics MeSH
- Carcinoma, Pancreatic Ductal genetics metabolism pathology MeSH
- Gene Expression MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger genetics metabolism MeSH
- Mutation MeSH
- Pancreatic Neoplasms genetics metabolism pathology MeSH
- Pancreas metabolism MeSH
- Proto-Oncogene Proteins p21(ras) MeSH
- Proto-Oncogene Proteins genetics MeSH
- ras Proteins genetics MeSH
- RNA, Neoplasm genetics metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- KRAS protein, human MeSH Browser
- RNA, Messenger MeSH
- Proto-Oncogene Proteins p21(ras) MeSH
- Proto-Oncogene Proteins MeSH
- ras Proteins MeSH
- RNA, Neoplasm MeSH
OBJECTIVES: The aim of this study was to evaluate transcript levels of all 49 human ATP-binding cassette transporters (ABCs) in one of the most drug-resistant cancers, namely, the pancreatic ductal adenocarcinoma (PDAC). Association of ABCs levels with clinical-pathologic characteristics and KRAS mutation status was followed as well. METHODS: Tumors and adjacent nonneoplastic tissues were obtained from 32 histologically verified PDAC patients. The transcript profile of ABCs was assessed using quantitative real-time polymerase chain reaction with a relative standard curve. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing. RESULTS: Most ABCs were deregulated in PDAC and 10 ABCs were associated with clinical-pathologic characteristics. KRAS mutations did not change the global expression profile of ABCs. CONCLUSIONS: The expression of ABC transporters was significantly deregulated in PDAC tumors when compared to nonmalignant tissues. The observed up-regulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2 in tumors may contribute to the generally poor treatment response of PDAC. The up-regulation of ABCA1, ABCA7, and ABCG1 implicates a serious impairment of cellular cholesterol homeostasis in PDAC. On the other hand, the observed down-regulation of ABCA3, ABCC6, ABCC7, and ABCC8 suggests a possible role of stem cells in the development and progression of PDAC.
References provided by Crossref.org
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Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes
ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer
Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216
FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy
