ABSTRACT
BACKGROUND: Multiple drug resistance (MDR), both inherent and acquired, is a serious problem in non-small cell lung carcinomas (NSCLC). The purpose of this study was to investigate the prevalence of expression of genes encoding drug efflux pumps, MDR1 and MRP-1, at both the mRNA and protein levels, in this type of cancer. MATERIALS AND METHODS: Tumour specimens (38 cases) were analysed using immunohistochemistry and, where possible (30 cases), also using reverse-transcriptase polymerase chain reaction. RESULTS: The results from this analysis indicated that either, or both, drug efflux pumps were frequently expressed in NSCLC. Expression of mrp1 was found to be predominant over mdr1 at the mRNA level, while MDR1 P-gp was more frequently detected than MRP-1 protein. In some cases, proteins encoding pumps were detected without corresponding mRNAs--possibly due to differing sensitivities of the analysis techniques. CONCLUSION: Future studies of mdr1 and mrp1 using increased-sensitivity qPCR techniques, in parallel with protein analysis, in larger cohorts of cases may help to elucidate the role of drug efflux pumps in NSCLC multiple drug resistance.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Multidrug Resistance-Associated Proteins/biosynthesis , RNA, Messenger/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Middle Aged , Multidrug Resistance-Associated Proteins/genetics , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Ten sheep naturally affected with enzootic nasal adenocarcinoma (ENA), a disease associated with ovine enzootic nasal tumour virus (ENTV-1), were found also to be infected with jaagsiekte sheep retrovirus (JSRV), the causal agent of ovine pulmonary adenocarcinoma (OPA). Only one of the sheep showed OPA lung lesions. The animals belonged to 10 flocks located in a geographical area in which OPA is frequently seen. ENTV-1 was found in all the ENA tumours but only occasionally in extra-tumoral sites, confirming the results of a previous study. In contrast, JSRV had a disseminated tissue distribution, similar to that previously reported for animals infected with JSRV. However, the occurrence of JSRV in lymphoid tissues was clearly greater than in sheep infected with JSRV but with no lesions of ENA. The data suggested a synergistic relationship between ENTV-1 and JSRV, resulting in increased proliferation of JSRV.
