Comparison of the tyrosine kinase activity with the proliferation rate in human colon solid tumors and tumor cell lines.

Abstract

The role of the tyrosine kinase signal transduction pathway was investigated in human colon solid tumors and colon tumor cell lines. A high level of tyrosine kinase activity was found in 7 of the 27 human solid tumors tested (26%). In these cases, a close correlation between the level of tyrosine kinase activity and the high ratio of the S phase cells has been demonstrated (r = 0.8418). High autophosphorylation accompanied by a high proliferation capacity was detected in 8 cases (29.6%). In 12 cases (44%) low tyrosine kinase activity with a lower proliferation rate was found. Seven of the 8 human colon tumor cell lines tested showed tyrosine kinase activity. Differentiation-inducing agents, such as sodium butyrate and retinoic acid, have been applied to influence the rate of cell proliferation. Treatment with 5 mM sodium butyrate (24 h) and 10 microM retinoic acid (48 h) effectively decreased the fraction of S phase cells and 3H-thymidine incorporation. The tyrosine kinase activity fell to 9-22% and to 44-65% of the original value in the case of the sodium butyrate and retinoic acid treatment, respectively. Our results suggest that a significant part of human colon tumors have an active tyrosine kinase signal transduction pathway and that tyrosine kinase plays a role in the process of proliferation rather than in the process of differentiation in these human colon tumor cell lines.