Steroid hormone receptor characterization of several histologic variants of a rat prostatic adenocarcinoma

Abstract

Several histologic variants of the transplantable R-3327 prostatic adenocarcinoma carried in male Copenhagen rats have been characterized and the histologic types have been correlated with steroid hormone receptor content. One type is clearly an adenocarcinoma; this tumor is hormonally responsive and contains substantial amounts of both androgen and estrogen receptors. In contrast, another histologic type, a fibrosarcoma, is hormonally nonresponsive and does not contain either receptor. A third histologic variant is classified as a carcinosarcoma and contains histological elements of both adenocarcinoma and fibrosarcoma and is also hormonally responsive. This tumor contains lower receptor levels than the adenocarcinomas but more than the fibrosarcomas. The androgen receptor appears to be identical in the different histologic forms of the tumor: the sedimentation coefficient is 7.8S and the dissociatiln constant for methyltrienolone is 4 x 10(-9) M. Similarly, the estrogen receptor from the different histologic forms of the tumor has a sedimentation coefficient of 8.3S and the dissociation constant for estradiol is 7 x 10(-10) M. These findings clearly distinguish the cytosol binding macromolecules from plasma binding proteins, and classify them as steroid hormone receptors. Further, rat serum was devoid of androgen and estrogen binding in the 8S region. Normal prostate tissue from Copenhagen rats contained low levels of an androgen receptor, but no estrogen receptor. It is possible that during growth and/or passage of the R-3327 tumor, the hormonally responsive adenocarcinoma cells do not survive and there is a gradual emergence of the nonresponsive fibrosarcoma. If, as we suspect, the receptors are found in the epithelial cells and not the stromal cells, there clearly should be considerable variation of receptor content in the different intermediary histologic forms of the tumor.