RESUMO
BACKGROUND: The aim of this study was to elucidate the features of the expression of matrix metalloproteinases inducer-EMMPRIN (EMN) and matrix metalloproteinase 1 (MMP-1) in cell lines and in clinical samples of cervical squamous cell carcinoma (SCC). MATERIAL AND METHODS: The study was carried out using RT-PCR, densitometry and immunohistochemical studies (IHC) on commercial cell lines Siha, Caski, transformed with HPV16; HeLa, and C33A transformed with HPV18, line C33A without HPV, and in clinical samples of SCC and morphologically normal tissue adjacent to the tumor. RESULTS: The data obtained indicate that the expression of mRNA EMN and MMP-1 occurs in all cell lines at different levels. HPV type and number of genes copies had no effect on expression degree both EMN and MMP-1. Gene expression of EMN and MMP-1 has been investigated in tumor and normal tissues. MMP-1 expression in tumor tissue in SCC, as a rule, has been significantly increased (2-6 times) compared to normal tissue. It was found in 90% of tumor samples. It is known, that MMP-1 promotes the development of invasive and metastatic processes. EMN expression was lower in the tumor tissue than in normal tissue in most cases. An increase in EMN expression was noted only in some cases of SCC. CONCLUSION: The data obtained indicate that MMP-1 can serve as a marker of the invasive potential of SCC. EMN, apparently, is not a major factor responsible for MMP-1 expression in SCC. Data are important for understanding the process of tumor development and may have prognostic value for the patient.
Assuntos
Basigina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Neoplasias do Colo do Útero/metabolismo , Basigina/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 1 da Matriz/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
The prediction of biological activity spectra for substances as an approach for searching compounds with complex mechanisms of action was studied. New compounds with dual mechanisms of antihypertensive action were found by this approach. Biological activity spectra for substances were predicted on the basis of their structural formulas by the computer program PASS. Thirty molecular mechanisms of action of compounds from the MDDR 99.2 database, which cause the antihypertensive effect and can be predicted by PASS, have been identified. The analysis of predictions for compounds with 15 dual antihypertensive mechanisms of action from the MDDR 99.2 database has confirmed high accuracy of prediction. This approach was applied to databases of commercially available compounds (AsInEx and ChemBridge) and allowed us to select four substances that are potential inhibitors of angiotensin converting enzyme (ACE) and of neutral endopeptidase (NEP). At a later time, all these compounds were found to be the inhibitors of both ACE and NEP. The most potent compounds had IC(50) of 10(-7)-10(-9) M for ACE and 10(-5) M for NEP. New combinations of dual mechanisms of action never before found for antihypertensive compounds were predicted.