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Mechanisms of Cell Transformation in the Syrian Hamster Embryo (SHE) Cell Transformation System
Author(s) -
ISFORT ROBERT J.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06871.x
Subject(s) - neoplastic transformation , platelet derived growth factor receptor , growth factor , cell growth , biology , basic fibroblast growth factor , microbiology and biotechnology , cell , population , fibroblast growth factor , platelet derived growth factor , epidermal growth factor , transformation (genetics) , malignant transformation , chemistry , cancer research , cell culture , carcinogenesis , genetics , cancer , receptor , medicine , environmental health , gene
A bstract : The Syrian hamster embryo (SHE) cell transformation system has been used for investigational studies of basic mechanisms of neoplastic transformation, as well as determining the carcinogenic potential of chemical, physical, and biological agents. Many of these investigations utilize an intermediate step in the SHE cell neoplastic transformation process, known as morphological transformation, as an indicator that the cells have acquired an increased potential to progress to malignancy. While the nature of the morphologically transformed phenotype is not completely understood, it is believed to result from a block in the cellular differentiation of stem cells present within the SHE cell population. In terms of determination of the transforming potential of biological/chemical/physical agents, more than 500 agents have been tested in the SHE cell transformation assay with an 80–90% correlation between MT and carcinogenic potential. As such, the SHE cell transformation assay has utility as a test to provide short‐term information on the carcinogenic potential of chemicals. One class of agents of current interest with regard to SHE cell transformation assay utilization consists of growth and differentiation factors (GDFs). Analysis of the SHE cell transformation potential of the GDFs, epidermal growth factor (EGF), fibroblast growth factor 4 (FGF‐4), platelet‐derived growth factor AA (PDGF AA), PDGF AB, PDGF BB, and the antimitogenic GDF, transforming growth factor beta one (TGF‐β1), was performed. All GDFs, with the exception of TGF‐β1, induced SHE cell transformation. However, an interesting difference between the GDFs was observed‐PDGF A/B and PDGF B/B, but not PDGF A/A, EGF, or FGF‐4, induced transformation after both a transient 1‐day exposure and a continuous 7‐day exposure, while continuous 7‐day exposure was required for transformation by PDGF A/A, EGF, and FGF‐4. interestingly, both transient 1‐day and continuous 7‐day TGF‐β1 exposure resulted in suppression of transformation induced by a variety of transforming agents including growth factors, Ames assay‐positive carcinogens, Ames assay‐negative carcinogens, and spontaneous transformation. Interestingly TGF‐β1 was not able to suppress transformation by the tumor promoter, TPA. Together, these data demonstrate the utility of the Syrian hamster embryo cell transformation system for analyzing the transforming potential of GDFs and for characterizing differences in transforming mechanisms between different GDFs.