Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Androgen-Dependent Expression of the Gastrin-Releasing Peptide Receptor in Human Prostate Tumor Xenografts
Ist Teil von
The Journal of nuclear medicine (1978), 2007-01, Vol.48 (1), p.88-93
Ort / Verlag
United States: Soc Nuclear Med
Erscheinungsjahr
2007
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observation suggests that GRP receptors may be used as new visualization and treatment modalities for these tumors. Radiolabeled GRP receptor-targeting analogs of GRP and bombesin (BN) have successfully been developed for these purposes. Expression of GRP receptors in human prostate tumors is, however, primarily evaluated in early stages of tumor development and information on expression in the more progressive prostate tumors is uncertain. To evaluate GRP receptor expression in all stages of PC, we investigated GRP receptor expression using a panel of 12 established human PC xenograft models representing the different stages of human PC and the effect of antiandrogen treatment (castration).
Human PC xenografts were grown in male nude mice, and GRP receptor density in the tumors was evaluated using displacement receptor autoradiography with the universal BN receptor analog (125)I-[D-Tyr(6),beta-Ala(11),Phe(13),Nle(14)]BN(6-14) and the BN analog (111)In-[DTPA-Pro(1),Tyr(4)]BN (DTPA is diethylenetriaminepentaacetic acid) before and after castration.
Autoradiography showed high-density GRP receptor expression in the androgen-dependent tumors (3/12 models), whereas only very low receptor expression was found in the androgen-responsive and -independent tumors (9/12 models). Castration resulted in GRP receptor downregulation (11%-36% of initial values) in the 3 androgen-dependent tumors.
High GRP receptor density was only observed in androgen-dependent PC xenografts, indicating high GRP receptor expression in the early, androgen-dependent, stages of prostate tumor development and not in later stages. In addition, castration strongly reduced GRP receptor expression in androgen-dependent tumors, indicating that GRP receptor expression in human PC is androgen-regulated.