P-glycoprotein associated expression of c-fos and c-jun products in human lung carcinomas.
Surgical specimens of non-small cell lung carcinomas of 167 previously untreated patients were analyzed for expression of c-fos, c-jun, c-myc and c-neu products and for resistance to drugs. Because most of the patients were treated only by surgery, an in vitro test was used to determine the resistance. For the detection of the oncoproteins the streptavidin-biotin-peroxidase-complex method was used. An association between the resistance and c-fos and c-jun proteins was found (c-fos p = 0.01, c-jun p = 0.09), whereas a correlation between resistance and expression of c-neu and c-myc products was not observed. P-glycoprotein 170 was detected immunohistochemically in 91 tumors using the monoclonal antibody JSB-1. There was a significant correlation between the resistance measured by the in vitro test and P-glycoprotein 170 expression (p < 0.001). Also a significant correlation between the c-fos and c-jun proteins and the expression of P-glycoprotein was found (c-fos p = 0.017, c-jun p = 0.036). In contrast, no significant relationship was found between the expression of the c-neu or c-myc products and the expression of P-glycoprotein 170. Thus, there exists a significant relationship between resistance, P-glycoprotein 170, and c-fos and c-jun products in human non-small cell lung carcinomas. P-glycoprotein 170 may be regulated by the c-fos/c-jun protein complex, which binds specifically to AP-1.
Volm
M
M
German Cancer Research Center, Heidelberg.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D004317:Doxorubicin; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases