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Tumour promoter alone induces neoplastic transformation of fibroblasts from humans genetically predisposed to cancer.
Metadata
Journalnature42.778Date
1979-Dec-06
Type
Research Support, U.S. Gov't, P.H.S.
Journal Article
Volume
1979-Dec-06 / 282 : 619-21
Author
Kopelovich L , Bias NE , Helson L
DoiPMIDMESH
Animals
Cell Adhesion
Cell Transformation, Neoplastic
Eye
Humans
Mice
Mice, Nude
Multiple Endocrine Neoplasia
Neoplasm Transplantation
Neoplasms, Experimental
Phorbols
Tetradecanoylphorbol Acetate
Abstract
Neoplastic transformation is a multi-phase process apparently caused by carcinogens and subject to the influence of promoters. The naturally occurring phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) are potent tumour promoting agents. Through the use of phorbol esters a two-stage process of malignant transformation has been demonstrated in the mouse skin model and, more recently, in cell culture systems. Studies in vitro suggest that TPA reversibly inhibits terminal differentiation in most, but not all model systems, and that its function is presumably to increase the probability of expression of the malignant phenotype. We have studied the effects of TPA on mutant human fibroblast cell strains derived from individuals with hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait. We have previously demonstrated in these fibroblasts abnormal phenotypic expressions which often appear in transformed cells. In these studies, we have assumed that the ACR cell exists in an "initiated state" due to a dominant mutation and that expression of the malignant state might only require treatment with a promoting agent. This single experimental protocol provided a novel system for the study of cancer promotion in vitro. We have now demonstrated, for the first time, the growth in vivo of human mutant cells exposed to TPA alone.
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Naturenature
Metadata
LocationEngland
FromNATURE PUBLISHING GROUP

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