The presence of binding proteins for retinoic acid and dihydrotestosterone in murine and human colon tumors.

Abstract

Retinoic acid-binding protein (RABP), which is distinctly present in embryonic colon and lung, is below the limits of detection in adult mouse colon and lung. The binding protein is present in malignant murine colon tumors as well as in lungs of animals bearing subcutaneously implanted tumors. Primary cell cultures from 1 g of colon tumor 26 gave rise to about 10(7) tumor cells and yielded 30 mg of extractable protein. The lower limit for detection of RABP, based on the appearance of its specific 2S peak after sucrose density gradient sedimentation, was 0.1 mg of protein, which corresponds to 3.3 x 10(4) tumor cells. After subcutaneous implantation of colon tumor 26 in mice, no RABP peak was evident in the lung extracts up to the fourth day. From the fifth day onwards, RABP appeared in lung extracts, possibly as a consequence of pulmonary metastasis. Fragments of mouse lungs containing the metastatic tumor foci were reimplanted subcutaneously and produced tumors that contained RABP at levels comparable to those in colon tumor 26. The primary subcutaneous tumors and pulmonary metastatic tumors showed the same histologic appearance--an undifferentiated carcinoma. On the 15th day of subcutaneous implantation of colon tumor 26 in mice, RABP was detected in lung and brain but in none of the other tissues where the protein is normally undetectable. After intraperitoneal implantation of colon tumor 26 in mice, no well-defined RABP peaks were detected from their liver extracts. None of the three normal human colon extracts analyzed for RABP or a dihydrotestosterone-binding protein (DHTBP) contained any detectable amounts of either of the binding proteins. However, 70% of the human colon tumors contained RABP and 90% contained DHTBP. Both of these binding proteins were evident in the two human colon tissues adjoining colon tumors.