Cytochromes P450 and ABC-transporters gene expression profiling in dog osteosarcoma, mast cell, and mammary tumours

Introduction: Members of the cytochromes P450 (CYPs) superfamily of drug metabolizing enzymes play an outstanding role in bioactivation and/or inactivation processes of anticancer drugs and procarcinogens. Likewise, ABC-transporters (ABCTs) are considered of relevant importance in multidrug resistance phenomena. In humans, the presence of CYPs and ABCTs has been demonstrated, in tumour and non-tumours tissues, by using immunohistochemistry. On the other hand, scarce information have been published in the dog. Thus, aim of this study was to evaluate the expression of CYPs and ABCTs in canine neoplasias. Materials and Methods: Surgical biopsies of 25 canine mammary tumors, 40 mast cell tumours, 6 osteosarcoma as well as control samples from pathogen-free Beagles or euthanized dogs were collected. Quantitative Real Time PCR assays for canine CYP1A1, CYP1A2, CYP1B1, CYP2B11, CYP2C21, CYP2D15, CYP3A12, MDR1 (PgP), MRP1, MRP2, MRP3, and 2 housekeeping genes were set up by using UPL probes. Finally, the differential expression of target genes was evaluated between normal and tumour samples. Results: Generally, CYP1A1, CYP1A2, CYP2B11, CYP2C21 and CYP2D15 mRNA expression was strongly inhibited in tumour specimens compared to the respective normal tissues. CYP3A12 mRNA was increased 5-fold in osteosarcoma, while CYP1B1 was generally over expressed in almost all tumour samples. Among ABCTs, PgP and MRP3 were generally induced in tumour specimens. Conclusions: Results suggest that CYPs mRNA general inhibition in tumour samples confirm the potential usefulness of gene pro-drug therapy with CYPs involved in anticancer drugs metabolism. On the contrary, CYP1B1 and CYP3A12 could be proposed as potential biomarker of outcome in dog tumours, likewise to humans.