Expression of
estramustine-binding protein (
EMBP) was determined in eight variants of the Dunning R3327 rat prostate
adenocarcinoma. This secretory
protein was previously isolated from the normal rat prostate and binds
estramustine and
estromustine, the metabolites exerting anti-mitotic and anti-proliferative activity of the
anticancer agent estramustine phosphate (EstracytR).
EMBP was found in relatively high amounts only in the
androgen-responsive G and H
tumors from intact hosts, whereas low (AT-1, HI-F) or nondetectable levels (HI-S, AT-3, MAT-LyLu, MAT-Lu) were obtained in the
androgen-independent
tumors.
Castration decreased
EMBP expression in both G and H
tumors, as did
estradiol and
estramustine when given separately to intact rats. Supplementation of castrates with exogenous
androgen stimulated
EMBP expression above the pre-
castration level and was further enhanced when combined with
estradiol and in particular
estramustine. Partial physicochemical characterization of
EMBP in G and H
tumors was performed by using
ligand-based and immunoblotting techniques. [3H]
Estromustine was bound to cytosols and
salt extracts from
tumors with the same affinity and displayed similar surface-charge distribution, sedimentation behavior, and subunit composition as found for ventral and dorsolateral prostatic tissue from
tumor-bearing rats. This study indicates that the synthesis of
EMBP is under androgenic control and that its expression may be correlated to
androgen responsiveness, metastatic potential, and
androgen receptor content but not to growth rate and morphology of the
tumors.
EMBP may therefore provide a mechanism for concentration of cytotoxic activity at the target site in
EMBP-positive
tumors and help in the evaluation of antitumor effects obtained when administering
estramustine.