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 components 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 varible. 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 components, each eluting at a different ionic strength. Clinical correlations of objective remissions in breast cancer patients 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 uresponsive neoplasms.
Presented at the John E. Fogarty International Center, Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md. Supported in part by USPHS Grant CA-12836 from the National ancer Institute and a contract from the Southeastern Cancer Study Group.