Correlation between successful heterotransplantation of lung tumors in nude mice, poor prognosis of patients and expression of Fos, Jun, ErbB1, and Ras.
In order to examine whether the expression of the oncoproteins might be important for the malignancy of tumors, the relationship between the take rate of 88 human squamous cell lung carcinomas in nude mice and the expression of protooncogene products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and c-myc at the protein level was investigated by immunohistochemistry. Tumor take was assumed if within three months growing nodules were detected and confirmed histologically. The take rate of squamous cell lung carcinomas in nude mice was 49%. Sixty-eight percent of the tumors were positive for Fos, 40% for Jun, 67% for Ras, 77% for ErbB1, 35% for Neu and 39% for Myc. Tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had a significantly higher take rate in nude mice than tumors without an (over)expression of the oncogene products. In contrast, the expression of the c-neu and the c-myc genes at the protein level had no influence on the take rate of the tumors in nude mice. Interestingly, only patients with tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had significantly shorter survival times than patients whose tumors did not show an (over) expression of the oncogene products. These results demonstrate that the aggressiveness of the tumors visible in the higher take rate of the tumors in nude mice and in the shorter survival times of patients can be detected by measurement of the expression of c-fos, c-jun, c-erbB1 and c-ras at the protein level.
Volm
M
M
German Cancer Research Center, Heidelberg.
Mattern
J
J
D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D011519:Proto-Oncogenes; D016019:Survival Analysis; D014183:Transplantation, Heterologous
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)