Expression of genes involved in chemoresistance, proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome.
This study investigated the multidrug resistance, proliferation and apoptosis expression in renal cell carcinomas compared to adjacent normal kidney (ANK) tissues. Multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi), Topoisomerase-II alpha (TOPO-IIalpha), thymidylate synthase (TS), thymidine kinase (TK), Ki67, BAX and BCL-2 genes were analysed in a series of 30 renal cell carcinomas (RCC) and 16 biopsies from adjacent normal kidney (ANK) tissue using reverse-transcription-PCR (rt-PCR). The mean MDR1 expression was significantly lower in RCC than that of ANK (0.4 +/- 0.2 sd versus 0.75 +/- 0.19, p = 0.0008). The expression of MRP, GST-pi and TOPO-IIalpha was not significantly different in RCC as compared with ANK. The mean TK expression in RCC was significantly higher than in ANK (0.31 +/- 0.15 versus 0.09 +/- 0.08, p = 0.002). The TS and Ki67 expression in RCC was significantly higher than in ANK (87.5%, IC95% 71-100% versus 0%, p = 0.001; 56% IC95% 32-81% versus 0%, p = 0.004, respectively). BAX and BCL-2 expression in RCC was significantly higher than that of ANK (0.51 +/- 0.08 versus 0.18 +/- 0.12, p = 0.0001; 0.73 +/- 0.16 versus 0.5 +/- 0.22, p = 0.01, respectively). No significant correlation was found between MDR1, MRP, GST-pi, TOPO-IIalpha, TS, TK and BAX expression with the grade and the clinical stage in RCC.
Oudard
Stephane
S
Hôpital Européen Georges Pompidou, Division of Oncology, Paris, France. stephane.oudard@hop.egp.ap-hop-paris.fr
Levalois
Cecile
C
Andrieu
Jean-Marie
JM
Bougaran
Joelle
J
Validire
Pierre
P
Thiounn
Nicolas
N
Poupon
Marie-France
MF
Fourme
Emmanuelle
E
Chevillard
Sylvie
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002455:Cell Division / Q000235:genetics; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C494826:BAX protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013937:Thymidine Kinase