c-Ha-ras-I oncogene-induced differentiation and natural killer cell resistance in a human colorectal carcinoma cell line

Natural killer (NK) activity is primarily a peripheral blood function of a lymphocyte population capable of spontaneous lysis of many transformed and metastatic targets. However, NK-susceptible targets tend to be relatively poorly differentiated. We have previously shown that poorly differentiated h...

Full description

Saved in:
Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 50; no. 8; pp. 2518 - 2523
Main Authors Bagli, D J, D'Emilia, J C, Summerhayes, I C, Steele, G D, Barlozzari, T
Format Journal Article
LanguageEnglish
Published United States 15.04.1990
Subjects
Blotting, Western
Cell Line
Clone Cells
Colorectal Neoplasms - genetics
Colorectal Neoplasms - immunology
Colorectal Neoplasms - pathology
Cytotoxicity, Immunologic
Fluorescent Antibody Technique
Genes, ras
HLA Antigens - analysis
Humans
Killer Cells, Natural - immunology
Oncogene Protein p21(ras) - analysis
Tumor Cells, Cultured - cytology
Tumor Cells, Cultured - immunology
Online AccessGet full text

Cover

More Information
Summary:Natural killer (NK) activity is primarily a peripheral blood function of a lymphocyte population capable of spontaneous lysis of many transformed and metastatic targets. However, NK-susceptible targets tend to be relatively poorly differentiated. We have previously shown that poorly differentiated human colorectal carcinoma are lysed by NK cells. Well-differentiated and chemically differentiated colorectal carcinomas are insensitive to NK lysis. The present study demonstrates that transfection of the c-Ha-ras-I oncogene into a poorly differentiated colorectal carcinoma cell line also renders it NK resistant. This resistance is accompanied by a more differentiated colorectal carcinoma phenotype. Two ras-transfected lines (Clone-A-5 and Clone-A-4) showed a 30-66% decrease in susceptibility to NK lysis as compared to the parental line in standard cytotoxicity assays. The resistance of these transfectants was strictly dependent on expression of the activated p21, the H-ras protein product. Studies to assess the integrity of the initial binding step in NK lysis showed a significant decrease in the ability of these transfectants to form conjugates with fresh NK cells. It is likely that transfection with c-Ha-ras-I has selectively modulated critical NK target recognition structures.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0008-5472