Differential expression of cytochrome P450 enzymes in normal and tumor tissues from childhood rhabdomyosarcoma.
Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.
Instituto Nacional de Pediatría, Mexico City, Mexico.
Dora
D
Molina-Ortiz
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Rafael
R
Camacho-Carranza
Instituto Nacional de Pediatría, Mexico City, Mexico.
José Francisco
JF
González-Zamora
Centro Nacional para la Prevención y el Tratamiento del Cáncer en la Infancia y la Adolescencia (CeNSIA), Mexico City, Mexico.
Jaime
J
Shalkow-Kalincovstein
Instituto Nacional de Pediatría, Mexico City, Mexico.
Rocío
R
Cárdenas-Cardós
Instituto Nacional de Pediatría, Mexico City, Mexico.
Rosario
R
Ností-Palacios
Instituto Nacional de Pediatría, Mexico City, Mexico.
Araceli
A
Vences-Mejía
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000378:metabolism*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; C585496:CYP1B1 protein, human; C509336:CYP2W1 protein, human; C510164:CYP3A5 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; C510163:CYP3A4 protein, human