Autor: |
Gentile LB; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Nagamine MK; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Biondi LR; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Sanches DS; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Toyota F; Veterinary Hospital Cães e Gatos, Osasco, São Paulo, Brazil., Giovani TM; Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo (USP), São Paulo, São Paulo, Brazil., de Jesus IP; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., da Fonseca IIM; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Queiroz-Hazarbassanov N; Applied Pharmacology and Toxicology Laboratory, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Diaz BL; Laboratory of Inflammation, Carlos Chagas Filho Biophysics Institute (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, Brazil., Salles Gomes COM; Applied Pharmacology and Toxicology Laboratory, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil., Dagli MLZ; Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, São Paulo, Brazil. |
Abstrakt: |
There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development. |