Andersen Vibeke, Vogel Lotte K, Kopp Tine Iskov, Sæbø Mona, Nonboe Annika W, Hamfjord Julian, Kure Elin H, Vogel Ulla
Organ Center, Hospital of Southern Jutland, Aabenraa, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; Medical Department, Regional Hospital Viborg, Viborg, Denmark.
Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2015 Mar 20;10(3):e0119255. doi: 10.1371/journal.pone.0119255. eCollection 2015.
Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds across the epithelial barrier. Low mRNA level of ABCB1 has previously been identified as an early event in colorectal carcinogenesis (Andersen et al., PLoS One. 2013 Aug 19;8(8):e72119). ABCC2 and ABCG2 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 106 adenoma cases (12 with severe dysplasia, 94 with mild-moderate dysplasia) and from 18 controls with normal endoscopy. We found significantly higher level of ABCC2 in adenomas with mild to moderate dysplasia and carcinoma tissue compared to the levels in unaffected tissue from the same individual (P = 0.037, P = 0.037, and P<0.0001) and in carcinoma and distant unaffected tissue from CRC cases compared to the level in the healthy individuals (P = 0.0046 and P = 0.036). Furthermore, ABCG2 mRNA levels were significantly lower in adenomas and carcinomas compared to the level in unaffected tissue from the same individuals and compared to tissue from healthy individuals (P<0.0001 for all). The level of ABCB2 in adjacent normal tissue was significantly higher than in tissue from healthy individuals (P = 0.011). In conclusion, this study found that ABCC2 and ABCG2 expression levels were altered already in mild/moderate dysplasia in carcinogenesis suggesting that these ABC transporters are involved in the early steps of carcinogenesis as previously reported for ABCB1. These results suggest that dysfunctional transport across the epithelial barrier may contribute to colorectal carcinogenesis.
结直肠癌（CRC）的发生可能源于饮食、肠道微生物和免疫系统之间的功能失调相互作用。ABC转运蛋白ABCB1（P-糖蛋白、多药耐药蛋白1、MDR1）、ABCC2（MRP2）和ABCG2（BCRP）参与多种化合物跨上皮屏障的转运。先前已确定ABCB1的低mRNA水平是结直肠癌发生的早期事件（Andersen等人，《公共科学图书馆·综合》。2013年8月19日；8(8):e72119）。对122例CRC病例、106例腺瘤病例（12例重度发育异常，94例轻度至中度发育异常）以及18例内镜检查正常的对照者的肠道组织进行了ABCC2和ABCG2 mRNA水平评估。我们发现，与同一人未受影响组织中的水平相比，轻度至中度发育异常的腺瘤和癌组织中ABCC2水平显著更高（P = 0.037、P = 0.037和P<0.0001），与健康个体相比，CRC病例的癌组织和远处未受影响组织中ABCC2水平也显著更高（P = 0.0046和P = 0.036）。此外，与同一人未受影响组织中的水平以及健康个体的组织相比，腺瘤和癌组织中ABCG2 mRNA水平显著更低（所有P<0.0001）。相邻正常组织中ABCB2水平显著高于健康个体的组织（P = 0.011）。总之，本研究发现，在致癌过程中，轻度/中度发育异常阶段ABCC2和ABCG2表达水平就已改变，表明这些ABC转运蛋白如先前报道的ABCB1一样参与致癌的早期步骤。这些结果表明，跨上皮屏障的转运功能失调可能促成结直肠癌的发生。
