Modulation of the transformed and neoplastic phenotype of rat fibroblasts by MHC-I gene expression

Transfection of the activated ras oncogene (Ha-ras) into second passage rat embryo fibroblasts can induce the metastatic phenotype, while cotransfection of Ha-ras with the adenovirus type 2 E1a gene (Ad2-E1a) yields cells which are tumorigenic but nonmetastatic in nude mice. Because of the presence...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1989-06, Vol.49 (12), p.3392-3395
Main Authors: GATTONI-CELLI, S, STRAUSS, R. M, WILLETT, C. G, POZZATTI, R, ISSELBACHER, K. J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Transformation, Neoplastic
Clone Cells
Fibroblasts - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genes, MHC Class I
Genes, ras
Histocompatibility Antigens Class I - genetics
Mice
Mice, Mutant Strains
Mice, Nude
Neoplasm Metastasis
Nucleic Acid Hybridization
Phenotype
Rats
T-Lymphocytes - immunology
Tissue, organ and graft immunology
Transfection
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transfection of the activated ras oncogene (Ha-ras) into second passage rat embryo fibroblasts can induce the metastatic phenotype, while cotransfection of Ha-ras with the adenovirus type 2 E1a gene (Ad2-E1a) yields cells which are tumorigenic but nonmetastatic in nude mice. Because of the presence in nude mice of natural killer cells and B-lymphocytes, which might account for the different metastatic behavior of single versus double transfectants, we used triple deficient mutants as recipient animals in tumorigenicity assays. These mice carry two additional mutations resulting in the deficiency of natural killer cells and activated B-lymphocytes. We observed that the rat embryo fibroblast transfectants exhibit the same metastatic behavior in nude as well as in triple deficient mice, indicating that natural killer and B-cells are not responsible for the observed difference in metastatic phenotype between Ha-ras and Ha-ras plus Ad2-E1a transfectants. Double transfectants were found to express higher levels of major histocompatibility complex class I genes and the degree of expression appeared to correlate inversely with in vitro and in vivo parameters such as the ability to grow in agar-containing semisolid media and rate of tumor formation in triple deficient mice. Our observations are consistent with the concept that expression of major histocompatibility class I genes may be involved in regulating and modifying cell behavior by mechanisms independent of their role in immune recognition.
ISSN:0008-5472
1538-7445