Cytoplasmic estrogen receptor in a pregnancy-dependent mouse mammary tumor (TPDMT-4) and related autonomous lines.

Transplantable TPDMT-4 mammary tumors are characterized by pregnancy dependence, growth during pregnancy, regression after delivery, and practically no growth in virgin animals. In this study, tumor pieces were treated with chemical carcinogens in vitro and serially transplanted in virgin mice with increasingly short intervals between passages. Two autonomous sublines were obtained utilizing 4-nitroquinoline 1-oxide (1 microgram/ml) and 20-methylcholanthrene (10 microgram/ml) and were designated as PIMT-4491 and PIMT-4673, respectively. PIMT-4673 tumors, very similar morphologically to the parent tumors, were composed of small cuboidal epithelial cells which occasionally formed acinar and glandular structures. PIMT-4491 showed similar morphology with groups of spindle cells at early generations but became more sarcomatous at later generations. Cytoplasmic estrogen receptor (ER) was examined by sucrose density and dextran-coated charcoal methods in newly established and parent tumors. ER was undetectable in PIMT-4673. PIMT-4491 had the same levels of ER as did parent tumors up to generation 21, when ER levels began to decrease gradually until they reached 5.1 fmol/mg cytosol protein at generation 50. In TPDMT-4, ER levels varied from 20 to 75 fmol/mg cytosol protein and were not related to growth behaviors. Effects on TPDMT-4 tumors of estradiol and progesterone alone or in combination were investigated at generations 1- and 33. Under all hormonal conditions, late-generation tumors grew better than early ones. ER levels were not significantly different in the two generations, although they tended to be slightly higher at the later generation. Apparent dissociation constants estimated by Scatchard plots were on the order of 10(-10) M in all ER-positive tumors.