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  • Title: Androgen-dependent expression of the gastrin-releasing peptide receptor in human prostate tumor xenografts.
    Author: de Visser M, van Weerden WM, de Ridder CM, Reneman S, Melis M, Krenning EP, de Jong M.
    Journal: J Nucl Med; 2007 Jan; 48(1):88-93. PubMed ID: 17204703.
    Abstract:
    UNLABELLED: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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