RESUMO
The epithelial growth factor receptors are transmembrane proteins with an important role in the neoplastic progression of tumors, and in this context, DCIS is an important phase in the progression of canine mammary tumors. Studies on the molecular profile and its relationship to a progression of canine mammary tumors are important to improve the treatment of patients and for a better understanding of canine mammary carcinogenesis. The aim of this study was to determine, by immunohistochemistry, the relation between the expression of EGFR, ErbB-2, ErbB-3, and ErbB-4 in 52 canine mammary gland DCIS with high and low histological grade. A positive correlation between histological grade and expression of membrane ErbB-2 and cytoplasmic ErbB-4 was observed. Increased ErbB-4 membrane expression was correlated with increased ErbB-3 expression in low and high-grade DCIS. Our data suggest that increased expression of ErbB-2 and ErbB-4 may be related to more aggressive DCIS and probabily involved with canine mammary neoplastic progression.
Assuntos
Carcinoma Intraductal não Infiltrante/veterinária , Doenças do Cão/fisiopatologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Animais , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/fisiopatologia , Doenças do Cão/diagnóstico , Cães , Regulação Neoplásica da Expressão GênicaRESUMO
The development of the mammary gland is a hormone-regulated event. Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation. Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer. Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland. Pregnant rats were orally exposed to vehicle, 5 µg DES/kg/day, or 0.5 or 50 µg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17ß-estradiol for 3 months. Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals. ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells. Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR. Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone. In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.
Assuntos
Compostos Benzidrílicos/efeitos adversos , Cisto Mamário/induzido quimicamente , Carcinoma Intraductal não Infiltrante/induzido quimicamente , Dietilestilbestrol/efeitos adversos , Estradiol/efeitos adversos , Glândulas Mamárias Animais/efeitos dos fármacos , Fenóis/efeitos adversos , Administração Oral , Animais , Compostos Benzidrílicos/administração & dosagem , Cisto Mamário/veterinária , Carcinoma Intraductal não Infiltrante/veterinária , Proliferação de Células/efeitos dos fármacos , Dietilestilbestrol/administração & dosagem , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Feminino , Ovariectomia , Fenóis/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Fatores de RiscoRESUMO
Caveolin-1 (Cav-1) is a structural protein present in invaginations of the cell membrane. In human breast cancer, the cav-1 gene is believed to be a tumor suppressor gene associated with inhibition of tumor metastasis. However, little is known about its expression, regulation and function in canine mammary tumors. Expression levels of cav-1 were investigated using real-time PCR and immunohistochemical detection with an anti-human Cav-1 antibody. Gene expression stability of different samples was analyzed using the geNorm software. Mammary tumors from 51 female dogs were compared to normal mammary tissue from 10 female dogs. Malignant mammary cells showed a loss of Cav-1 expression by quantitative RT-PCR and weak Cav-1 staining by immunohistochemistry compared to normal mammary gland tissue. There was a significant relationship between outcome and immunostaining as well as with tumor size, indicating that caveolin subexpression has a positive predictive value and is related to higher survival and smaller tumor size. Our findings indicate that Cav-1 is a potential prognostic marker for canine mammary tumors.