Expression of resistance factors (P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II) and their interrelationship to proto-oncogene products in renal cell carcinomas.
BACKGROUND
This study investigates whether or not an interrelationship exists between the expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase, topoisomerase II) and proto-oncogene products (c-fos, c-myc, c-K-ras, epidermal growth factor receptor [EGF-R], and c-neu proteins.)


METHODS
Thirty-eight human renal cell carcinomas of previously untreated patients were analyzed for expression of P-glycoprotein (P-170), glutathione S-transferase-pi (GST-pi), topoisomerase II (Topo II) and proto-oncogene proteins by means of immunohistochemistry. Because of significant heterogeneity in most tumor biopsies, all analyses were done on tumor-derived primary cell culture lines on the third or fourth passage.


RESULTS
An interrelationship between increased expression of P-170 and GST-pi and down-regulation of Topo II was found. Expression of the c-fos protein was seen in 66% of the tumors; expression of the c-myc protein, in 50%; of the c-K-ras protein, in 16%; of the EGF-R protein, in 61%; and of the c-neu protein, in 54% of the tumors. A significant correlation between the resistance factors and the c-fos, EGF-R, and c neu-proteins was observed (GST/c-fos, P = 0.012; Topo II/c-fos, P = 0.024; P-170/EGF-R, P < 0.001; GST/EGF-R, P = 0.018; Topo II/EGF-R, P = 0.027; P-170/c-neu, P = 0.005; GST/c-neu, P = 0.018; Topo II/EGF-R, P = 0.027; P-170/c-neu, P = 0.005; GST/c-neu, P = 0.008; Topo II/c-neu, P = 0.05). In contrast, interrelationships between resistance proteins and c-myc and c-K-ras proteins were not found. A significant interrelationship between the investigated resistance-related proteins or proto-oncogene proteins and the stage or grading of the tumors was not observed.


CONCLUSIONS
The results demonstrate that in renal cell carcinomas a significant relationship exists between resistance-related proteins, such as P-170, GST-pi, or Topo II, and proto-oncogenes, such as c-fos, c-erbB1, and c-neu.
Volm
M
M
German Cancer Research Center, Heidelberg.
Kästel
M
M
Mattern
J
J
Efferth
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004250:DNA Topoisomerases, Type II; D066246:ErbB Receptors; D005982:Glutathione Transferase; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; C000715470:MAS1 protein, human; C501009:HRAS protein, human