Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells.
The effects of butyrate-mediated differentiation of human colon carcinoma cells on the expression of src-related tyrosine protein kinases were analyzed. The results demonstrate that treatment of a variety of colon carcinoma cell lines with 2 mM sodium butyrate resulted in diminished population doubling rates, altered morphology, decreased anchorage-independent growth, and increased expression of colon epithelial differentiation marker enzymes such as alkaline phosphatase. In butyrate-treated cells, significantly diminished protein kinase activities and abundance of pp60c-src and p56lck were found to parallel the butyrate-induced phenotypic alterations. For the lck gene, the decreased levels in p56lck abundance were found to coincide with diminished levels of steady-state lck mRNAs. In contrast, treatments which arrested the growth of the colon carcinoma cells without inducing differentiation had no effect on the level of expression of these proteins. Furthermore, colon carcinoma cell lines which were found to be resistant to butyrate-induced differentiation showed no change in the kinase activity or abundance of either protein following butyrate treatment. These results indicate that the expression of several src-related kinases in human colon carcinoma can be influenced by the differentiation state of the cells.
Foss
F M
FM
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Veillette
A
A
Sartor
O
O
Rosen
N
N
Bolen
J B
JB
D000469:Alkaline Phosphatase / Q000032:analysis; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016392:Proto-Oncogene Proteins pp60(c-src); D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured
D002087:Butyrates; D011518:Proto-Oncogene Proteins; D020148:Butyric Acid; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016392:Proto-Oncogene Proteins pp60(c-src); D000469:Alkaline Phosphatase