RESUMO
INTRODUCTION: We evaluated the association between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type 1 (AT( 1))-receptor A1166C polymorphisms. METHODS: Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer. RESULTS: The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, chi(2)); and for AT(1)receptor were:AA,AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, chi( 2)).The results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls. CONCLUSIONS: The ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes.The ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible target for developing genetic markers for breast cancer.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Brasil , Estudos de Casos e Controles , Feminino , Deleção de Genes , Humanos , Pessoa de Meia-Idade , Mutagênese Insercional , Pós-Menopausa/genética , Pré-Menopausa/genéticaRESUMO
We described in mouse inner medullary-collecting duct cells (mIMCD-3) the somatic and the N-domain ACE synthesis and its interaction with the kallikrein-kinin system co-localized in the same cells. We purified two ACE forms from culture medium, M1 (130 kDa) and M2 (N-domain, 60 kDa), and cellular lysate, C1 (130 kDa) and C2 (N-domain, 60 kDa). Captopril and enalaprilat inhibited the purified enzymes. The immunofluorescence studies indicated that ACE is present in the membrane, cytoplasm and in the cell nucleus. Kinin B1 and B2 receptors were detected by immunofluorescence and showed to be activated by BK and DesR9 BK, increasing the acidification rate which was enhanced in the presence of enalaprilat. The presence of secreted and intracellular ACE in mIMCD-3 confirmed the hypothesis previously proposed by our group for a new site of ACE secretion in the collecting duct.
