Effects of adrenal androgens on the transplantable human prostate tumor PC-82.

Abstract

The potential of the adrenal androgens androstenedione (A) and dehydroepiandrosterone (DHEA) to stimulate prostate tumor growth was investigated in the hormone-dependent human prostate tumor model PC-82, propagated in nude mice. Substitution of castrated mice bearing growth-arrested tumors with DHEA for 28 days, resulting in peripheral levels of 9.2 +/- 1.7 nmol/liter (mean +/- SEM), led to a decline of tumor burden comparable to that observed in castrated controls. Intratumor testosterone (T) and 5 alpha-dihydrotestosterone were similar to those detected in the castrated group. In contrast, high-dose A supplementation (peripheral level of 13.5 +/- 1.3 nmol/liter) in androgen ablated tumor-bearing mice resulted in tumor growth, although less pronounced than in T-resubstituted mice (T level of 18.8 +/- 1.5 nmol/l). Intraprostatic levels of androgens were not different between both groups. Substitution of castrated PC-82 tumor-bearing mice with low-dose A (2.5 +/- 0.4 nmol/l) neither stimulated growth of tumors nor did it lead to regression of PC-82 tumors. Proliferative activity as estimated by BrdU incorporation (S-phase cells) was not induced in these tumors. In conclusion, DHEA does not have a stimulatory effect on growth of PC-82 tumor tissue, but A is capable of inducing PC-82 tumor growth, most likely through peripheral conversion of A into T and 5 alpha-dihydrotestosterone.

Targeting the relaxin hormonal pathway in prostate cancer

“…AR signalling plays a key role in regulating the development and growth of male reproductive organs and in reproductive organ function in both the male and female . AR maintains its involvement in the development and growth of prostate cancer, where AR activation promotes cell growth, angiogenesis and invasiveness . Therefore, androgens are attractive targets for therapeutic intervention.…”

Efecto de la dehidroepiandrosterona en las proteínas involucradas en la transición epitelio-mesénquima en células de cáncer de mama

“…En otros tipos de cáncer como el de próstata, se ha descrito que la DHEA no tiene efecto en el crecimiento de cáncer prostático humano trasplantado en ratones desnudos (Van Weerden et al, 1992), mientras que otro trabajo describe que la DHEA induce la proliferación de las células de cáncer de próstata LNCaP (Arnold et al, 2007).…”