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Molecular determinants of metastatic transformation.

In recent years, experimental systems have developed to analyze genetic and epigenetic regulation of the metastatic phenotype. Numerous studies have uncovered a potent role for transforming oncogenes in metastatic conversion. In addition, it has been shown that oncoprotein products operate in a dose...

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Detalles Bibliográficos
Autores principales: Egan, S E, Wright, J A, Greenberg, A H
Formato: Texto
Lenguaje:English
Publicado: 1991
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568036/
https://www.ncbi.nlm.nih.gov/pubmed/1773806
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author Egan, S E
Wright, J A
Greenberg, A H
author_facet Egan, S E
Wright, J A
Greenberg, A H
author_sort Egan, S E
collection PubMed
description In recent years, experimental systems have developed to analyze genetic and epigenetic regulation of the metastatic phenotype. Numerous studies have uncovered a potent role for transforming oncogenes in metastatic conversion. In addition, it has been shown that oncoprotein products operate in a dose-dependent fashion. The continued expression of oncoproteins is required to induce and regulate metastatic dissemination of tumor cells and, consequently, many of the signal transduction pathways that are controlled by the oncogene products can regulate metastasis. Exogenous growth factors that act through these same pathways also alter metastatic potential. Some primary and immortalized cells can be transformed by oncogenes but remain completely benign and nonmetastatic. Malignant transformation can be achieved in these cells through the cooperative interaction of specific oncogenes or loss of active suppression regulated by recessive genetic determinants. Therefore, it is likely that tumor cells acquire the metastatic phenotype through the cooperative interaction of dominant and recessive genetic alterations. This model is consistent with the correlative data accumulating in studies of human tumor specimens where more malignant carcinomas often contain both activating mutations in oncogenes and either inactivating mutations or loss of tumor-suppressor genes.
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spelling pubmed-15680362006-09-18 Molecular determinants of metastatic transformation. Egan, S E Wright, J A Greenberg, A H Environ Health Perspect Research Article In recent years, experimental systems have developed to analyze genetic and epigenetic regulation of the metastatic phenotype. Numerous studies have uncovered a potent role for transforming oncogenes in metastatic conversion. In addition, it has been shown that oncoprotein products operate in a dose-dependent fashion. The continued expression of oncoproteins is required to induce and regulate metastatic dissemination of tumor cells and, consequently, many of the signal transduction pathways that are controlled by the oncogene products can regulate metastasis. Exogenous growth factors that act through these same pathways also alter metastatic potential. Some primary and immortalized cells can be transformed by oncogenes but remain completely benign and nonmetastatic. Malignant transformation can be achieved in these cells through the cooperative interaction of specific oncogenes or loss of active suppression regulated by recessive genetic determinants. Therefore, it is likely that tumor cells acquire the metastatic phenotype through the cooperative interaction of dominant and recessive genetic alterations. This model is consistent with the correlative data accumulating in studies of human tumor specimens where more malignant carcinomas often contain both activating mutations in oncogenes and either inactivating mutations or loss of tumor-suppressor genes. 1991-06 /pmc/articles/PMC1568036/ /pubmed/1773806 Text en
spellingShingle Research Article
Egan, S E
Wright, J A
Greenberg, A H
Molecular determinants of metastatic transformation.
title Molecular determinants of metastatic transformation.
title_full Molecular determinants of metastatic transformation.
title_fullStr Molecular determinants of metastatic transformation.
title_full_unstemmed Molecular determinants of metastatic transformation.
title_short Molecular determinants of metastatic transformation.
title_sort molecular determinants of metastatic transformation.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568036/
https://www.ncbi.nlm.nih.gov/pubmed/1773806
work_keys_str_mv AT eganse moleculardeterminantsofmetastatictransformation
AT wrightja moleculardeterminantsofmetastatictransformation
AT greenbergah moleculardeterminantsofmetastatictransformation