Expression of P-glycoprotein, multidrug resistance-associated protein, glutathione-S-transferase pi and p53 in canine transmissible venereal tumor

Abstract

Pesq. Vet. Bras. 34(1):71-78, janeiro 2014 71 RESUMO.-[Expressão da glicoproteína-P, proteína associada à múltiplas drogas, glutationa-S-transferase pi e p53 no tumor venéreo transmissível canino.] A superexpressão das proteínas glicoproteína-P (Gp-P), proteína associada à resistência à múltiplas drogas 1 (MRP1) e p53 mutante e a enzima glutationa-S-transferase pi (GSTpi) está relacionada com resistência à quimioterapia em neoplasias humanas e caninas. Este estudo avaliou a expressão, por meio da imuno-histoquímica desses marcadores em espéci-mes de TVT caninos sem histórico de quimioterapia prévia (TVT1, n=9) e em TVT caninos que apresentaram resposta clínica insatisfatória ao sulfato de vincristina (TVT2, n=5). A porcentagem de espécimes positivos para Gp-P, MRP1, GSTpi e p53 foram, respectivamente 88,8%, 0%, 44,5% e 22,2% no grupo TVT1 e 80%, 0%, 80% e 0% no grupo TVT2. No TVT1, um espécime apresentou expressão positiva para três marcadores e quatro para dois marcadores. No TVT2, três espécimes expressaram a Gp-P e GSTpi. Em conclusão, os TVTs caninos estudados expressaram os quatro marcadores avaliados, no entanto apenas a Gp-P e GSTpi foram significativamente expressas, principalmente no citoplasmas e no citoplasma e no núcleo, respectivamente, The overexpression of proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1), mutant p53, and the enzyme glutathione-S-transferase (GSTpi) are related to resistance to chemotherapy in neoplasms. This study evaluated the expression of these markers by immunohistochemistry in two groups of canine TVT, without history of prior chemotherapy (TVT1, n=9) and in TVTs presented unsatisfactory clinical response to vincristine sulfate (TVT2, n=5). The percentage of specimens positively stained for P-gp, MRP1, GSTpi and p53 were, respectively 88.8%, 0%, 44.5% and 22.2% in TVT1 and 80%, 0%, 80% and 0% in TVT2. In TVT1, one specimen presented positive expression for three markers and four specimens for two markers. In TVT2, three specimens expressed P-gp and GSTpi. In conclusion, the canine TVTs studied expressed the four markers evaluated, but just P-gp and GSTpi were significantly expressed, mainly at cytoplasm and cytoplasm and nuclei, respectively, either before chemotherapy as after vincristine sulfate exposure. Future studies are needed to demonstrate the function of these two markers in conferring multidrug resistance (MDR) or predict the response to chemotherapy in canine TVT.

Cell cycle kinetics, apoptosis rates and gene expressions of MDR‐1, TP53, BCL‐2 and BAX in transmissible venereal tumour cells and their association with therapy response

“…The progressive increase of TVTs with high percentages of aggressiveness and variable response to chemotherapy, including resistance, is partially due to the high expression of p‐glycoprotein (Pgp) by tumour cells, which leads to the expulsion of chemotherapeutic . Thus, treatment cost increases, as do side effects such as anorexia, nephrotoxicity and myelosuppression.…”

Expressão Da Glicoproteína-P E Mrp1 Em Tecidos De Cães Com Leishmaniose Visceral

“…Também exibiram reatividade as amostras de cólon canino, sem alterações patológicas, que foram utilizados como controle positivo das reações, e todas as amostras dos animais do grupo controle. Embora estes clones tenham sido concebidos para uso em humanos e animais de laboratório, tecidos caninos também são reativos, como visto neste estudo e nos de Ginn (1996) e de Gerardi et al (2014).…”

“…8720-01) e anti-MRP1 (clone MRP1-Novocastra Laboratories Ltd, Newcastle, UK, Cód. NCL-MRP1) utilizados na imuno-histoquímica foram produzidos em camundongos contra antígenos humanos e seguiu-se a metodologia descrita por Gerardi et al (2014) com algumas modificações. A expressão da MRP1 e gp-P foram pesquisados em cortes de 3 m de espessura montados em lâminas pré-tratadas com Poly-L-lisina (Cód.…”

Possible mechanisms of transmissible cancers in Tasmanian devils

“…A fourth possible proposed mechanism may involve overexpression of the some chemotherapy resistance enzymes in transmissible tumors [24,25]. It has been reported that P-glycoprotein (P-gp) the efflux pump, and glutathione-S-transferase (GSTpi) which is associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis were significantly overexpressed in canine transmissible venereal tumor mainly at cytoplasm and nuclei and both of these proteins are associated with multidrug resistance to chemotherapy in neoplasms [25][26][27].…”

“…It has been reported that P-glycoprotein (P-gp) the efflux pump, and glutathione-S-transferase (GSTpi) which is associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis were significantly overexpressed in canine transmissible venereal tumor mainly at cytoplasm and nuclei and both of these proteins are associated with multidrug resistance to chemotherapy in neoplasms [25][26][27]. Telomerase is up-regulated in Tasmanian devil cancer cells but not in normal tissues.…”