RESUMO
Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.
Assuntos
Adenocarcinoma/patologia , Adenoma Pleomorfo/patologia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Neoplasias Parotídeas/patologia , Receptores de Fatores de Crescimento/análise , Adulto , Idoso , Carcinoma in Situ/patologia , Proliferação de Células , Corantes , Progressão da Doença , Células Epiteliais/patologia , Receptores ErbB/análise , Feminino , Fatores de Crescimento de Fibroblastos/análise , Fator de Crescimento de Hepatócito/análise , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Serina-Treonina Quinases/análise , Proteínas Proto-Oncogênicas c-met/análise , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/análise , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/análise , Receptor IGF Tipo 1/análise , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/análise , Neoplasias da Glândula Submandibular/patologia , Fator de Crescimento Transformador beta1/análiseRESUMO
We have studied the involvement of growth factors (GF), their receptors (GF-R) and oncogenes in modulating tumor growth in the medroxyprogesterone acetate (MPA)-induced mammary tumor model in BALB/c mice. We demonstrated the presence of both ligands of the insulin-like growth factor family (IGF-I, IGF-II) and the two types of receptors (IGF-RI, IGF-RII). MPA upregulated IGF-II mRNA and protein levels in hormone-dependent lines (MPA-D). The progression to a hormone-independent phenotype was accompanied by a high constitutive expression of IGF-II and by a significant decrease in IGF-IIR number. An antisense strategy used to evaluate the role of IGF in the MPA-induced growth of epithelial MPA-D cells showed that IGF mediate progestin-induced mammary tumor growth by autocrine/intracrine pathways. We also studied the role of heregulins (HRG), the recently identified ligands for the c-erbB3 and c-erbB4 oncogenes. HRG mRNA expression was restricted to tumors of ductal origin. MPA induced an in vivo up-regulation of HRG expression. Finally, we also found that MPA may be exerting its proliferative effect on MPA-D lines by inhibiting the expression of transforming growth factor beta 1, (TGF-beta 1) and the lack of expression of TGF-beta 1 in hormone-independent tumors may be related to the acquisition of autonomous growth.(Au)
Assuntos
Animais , Feminino , Camundongos , RESEARCH SUPPORT, NON-U.S. GOVT , Adenocarcinoma/metabolismo , Transformação Celular Neoplásica/metabolismo , Substâncias de Crescimento/análise , Neoplasias Mamárias Experimentais/metabolismo , Oncogenes/genética , Receptores de Fatores de Crescimento/análise , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/genética , Transformação Celular Neoplásica/genética , Fator de Crescimento Epidérmico/análise , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/genética , Acetato de Medroxiprogesterona , Camundongos Endogâmicos BALB C , Fator de Crescimento Transformador beta/análiseRESUMO
We have studied the involvement of growth factors (GF), their receptors (GF-R) and oncogenes in modulating tumor growth in the medroxyprogesterone acetate (MPA)-induced mammary tumor model in BALB/c mice. We demonstrated the presence of both ligands of the insulin-like growth factor family (IGF-I, IGF-II) and the two types of receptors (IGF-RI, IGF-RII). MPA upregulated IGF-II mRNA and protein levels in hormone-dependent lines (MPA-D). The progression to a hormone-independent phenotype was accompanied by a high constitutive expression of IGF-II and by a significant decrease in IGF-IIR number. An antisense strategy used to evaluate the role of IGF in the MPA-induced growth of epithelial MPA-D cells showed that IGF mediate progestin-induced mammary tumor growth by autocrine/intracrine pathways. We also studied the role of heregulins (HRG), the recently identified ligands for the c-erbB3 and c-erbB4 oncogenes. HRG mRNA expression was restricted to tumors of ductal origin. MPA induced an in vivo up-regulation of HRG expression. Finally, we also found that MPA may be exerting its proliferative effect on MPA-D lines by inhibiting the expression of transforming growth factor beta 1, (TGF-beta 1) and the lack of expression of TGF-beta 1 in hormone-independent tumors may be related to the acquisition of autonomous growth.