Gonadotropin-releasing hormone receptor-targeted gene therapy of gynecologic cancers.
The majority of ovarian, endometrial, and breast cancers express gonadotropin-releasing hormone (GnRH) receptors. Apart from reproductive organs (ovaries, fallopian tubes, and uterus) that are normally removed during surgical therapy of ovarian or endometrial cancer, pituitary gonadotrophs also express GnRH receptors. The signal transduction pathway in tumor cells is basically different from the classic GnRH receptor signal transduction, which is known to operate in the pituitary gonadotrophs and can therefore be considered tumor specific. Other organs and hematopoetic stem cells do not express GnRH receptors. We have recently shown specific activation of nucleus factor kappaB in ovarian, endometrial, and breast cancers after treatment with GnRH agonists. Based on this tumor-specific signaling pathway and the distribution pattern of GnRH receptors, we have developed and successfully tested a gene therapy concept by using a GnRH analogue as an inducer for the transcription of a therapeutic gene in cell culture and in nude mice.
Gründker
Carsten
C
Department of Gynecology and Obstetrics, Robert-Koch-Street 40, D-37099 Göttingen, Germany. grundker@med.uni-goettingen.de
Huschmand Nia
Abdohamid
A
Emons
Günter
G
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005833:Genital Neoplasms, Female / Q000628:therapy*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011355:Prodrugs / Q000494:pharmacology; D011966:Receptors, LHRH / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D017329:Triptorelin Pamoate / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D000998:Antiviral Agents; D016328:NF-kappa B; D011355:Prodrugs; D011966:Receptors, LHRH; D014157:Transcription Factors; D017329:Triptorelin Pamoate; D013937:Thymidine Kinase; D015774:Ganciclovir