Nuclear estrogen receptor and nonhistone chromosomal proteins in hormonal independency of murine breast cancers.

The capability of nuclear binding of cytosol estrogen receptors (ERc) was studied in GR mouse mammary tumors during their alteration of hormonal dependency through serial transplantations. Nuclei from GR mouse mammary tumors were incubated with uterine cytosol receptor complexes labeled with 125I-estradiol, and the amount of receptor binding in the 0.4 M KCl nuclear extracts was determined. The originally ERc-positive-hormone-dependent (type I) tumors were capable of nuclear receptor binding, while this function was markedly reduced in the evolved hormone-independent (type II) tumors, although the ERc content in the latter was still positive. The originally hormone-independent (ERc-negative, type III) tumors, however, retained the nuclear binding capability. It appears that the hormonal independency in type III tumors is due to a lack of ER, while in type II tumors it may be attributed to the loss of nuclear binding capability for receptor complexes. Nonhistone chromosomal proteins (NHCP) were analyzed by the 2-dimensional gel electrophoretic technique. A Mr 31,000 NHCP was present in 11 of 12 type I, and four of four type III tumors. Following serial transplantation of the type I tumors, this NHCP was either markedly diminished or not observed in all 14 type II tumors examined. Although it coincides with the capability of nuclear receptor binding, the biological function of this NHCP is still undefined and warrants further investigation.