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.
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 PDACpatients. 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 PDACtumors 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.
Authors: Rolando A R Villacis; Tatiane R Basso; Luisa M Canto; Maísa Pinheiro; Karina M Santiago; Juliana Giacomazzi; Cláudia A A de Paula; Dirce M Carraro; Patrícia Ashton-Prolla; Maria I Achatz; Silvia R Rogatto Journal: J Mol Med (Berl) Date: 2017-01-16 Impact factor: 4.599
Authors: M Oliverius; D Flasarova; B Mohelnikova-Duchonova; M Ehrlichova; V Hlavac; M Kocik; O Strouhal; P Dvorak; I Ojima; P Soucek Journal: Mutagenesis Date: 2019-12-19 Impact factor: 3.000
Authors: B Mohelnikova-Duchonova; M Kocik; B Duchonova; V Brynychova; M Oliverius; J Hlavsa; E Honsova; J Mazanec; Z Kala; I Ojima; D J Hughes; J E Doherty; H A Murray; M A Crockard; R Lemstrova; P Soucek Journal: Pharmacogenomics J Date: 2016-08-30 Impact factor: 3.550
Authors: Christopher Gromisch; Motaz Qadan; Mariana Albuquerque Machado; Kebin Liu; Yolonda Colson; Mark W Grinstaff Journal: Cancer Res Date: 2020-03-27 Impact factor: 12.701
Authors: Anke Van den Broeck; Hugo Vankelecom; Wouter Van Delm; Lies Gremeaux; Jasper Wouters; Joke Allemeersch; Olivier Govaere; Tania Roskams; Baki Topal Journal: PLoS One Date: 2013-09-17 Impact factor: 3.240