Loss of glucocorticoid receptors in B16BL6 murine melanoma associated with serial transplantation, metastatic selection and altered growth properties.

Glucocorticoid cytosolic receptors (GR) have been studied in both a primary and in a lung selected (metastatic) series of a B16BL6 murine melanoma. In the primary series tumour there was an initial increase in GR content from 40 to 95.6 fM mg-1 protein. GR levels then fell over the next 11 transplant generations to 10 fM mg-1 protein. In the metastatic series, in the course of six transplant generations, GR content of 73 fM mg-1 protein fell to below detectable levels, i.e. less than 5 fM mg-1 protein. Both the metastatic and primary series tumours showed a significant decrease in doubling times with increasing transplant generation. We therefore suggest that in the primary series tumours, after an initial phase of adaptation from tissue culture to in vivo conditions, the increased growth of the tumours is independent of the loss of hormonal control caused by a reduction in the glucocorticoid receptor content associated with serial transplantation. In the metastatically selected series of tumours, there appears to be a selective growth pressure brought about by the cyclic transplantation procedure which was also accompanied by an increase in metastatic ability.