Molecular Heterogeneity of Cytosolic Forms of Estrogen Receptors from Human Breast Tumors1

Molecular heterogeneity of estrogen receptors in cytosols from human breast carcinomas was demonstrated with regard to size and surface ionic charge. Following separation of the molecular forms of estrogen receptors into either the 8S or the 4S species by sedimentation on linear gradients of sucrose, diethylaminoethyl cellulose chromatography was used to fractionate the various com ponents in these receptors. Separation of the 8S species by diethylaminoethyl cellulose chromatography revealed a number of specific binding components, each eluting at a different ionic strength. The number of components as well as their relative specific estrogen-binding capacities were highly variable. At least five different species were identified on the basis of their elution at different ionic strengths. Estrogen-binding components eluted either in the wash buffer or at a KCI concentration of 0.02 to 0.05, 0.13 to 0.17, 0.18 to 0.21, or 0.3 M. The 4S form of the estrogen receptor separated into at least two compo nents, each eluting at a different ionic strength. Clinical correlations of objective remissions in breast cancer pa tients given hormonal therapy with the molecular species of estrogen receptors indicated that women with tumors containing the 8S form showed a greater likelihood of responding. Our findings with diethylaminoethyl cellulose chromatography suggest that the molecular composition of the 8S species of estrogen receptors from hormonally responsive tumors is different from that of certain unre sponsive neoplasms.