Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue

Abstract

This paper is the first part of a series of three describing a number of observations made on the PC-82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen-dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1-90 nmol/liter) has been levelled out by the use of T-containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC-82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC-82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC-82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC-82 tumor tissue. Androgen withdrawal from T-implanted, tumor-bearing female mice caused a rapid reduction (90% within one day) of the tissue-T and a slower decline (up to 90% within seven to ten days) of tissue-DHT concentrations.

Suppression of Prostate Epithelial Proliferation and Intraprostatic Progrowth Signaling in Transgenic Mice by a New Energy Restriction-Mimetic Agent

“…Despite 93.7% and 79.7% decreases in the free and total testosterone, respectively, these reductions were not statistically significant ( P > 0.05), in part, due to large variations in the testosterone concentrations of vehicle controls. This wide variation in the serum testosterone level, however, is in line with the reported range of 1 to 90 pg/mL in nude mice (27). …”

Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice. II. Tumor growth and androgen receptors

“…lA, C). Yet, a low amount of occupied receptors together with the physiological plasma T levels of the intact mice led to the growth of the PC-82 tumor, whereas in castrated animals growth of the tumor was completely impaired [18,22].…”

“…In the present study T capsules of 0.25 and 1.0 cm length were applied. Data about hormone levels in plasma and tumor tissue of implanted and intact tumor-bearing mice were published previously [22]. Some groups of PC-82 mice in the present study were injected subcutaneously with a high dose of T 1 h before sacrifice.…”

“…Plasma levels of T in intact male mice fluctuated considerably (Table I) [22]. In order to provide a more constant hormonal milieu for the transplanted tumor tissue, T-containing Silastic implants were used as exogenous sources of androgen.…”

“…In this system it was shown that in the various sublines a relationship exists between the responsiveness to androgen and the total AR levels [17]. Similarly, AR containing transplantable human prostatic carcinomas were described that have an androgenresponsive growth pattern [18-211. In the first paper of this series the PC-82 tumor model was described with respect to its androgen dependency and the effect of hormonal manipulation on androgen levels in the plasma and in the tumor tissue [22]. The PC-82 tumor contains an androgen binding protein with the characteristics described for AR present in prostate tissue [23].…”