RGD Reference Report - Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo. - Rat Genome Database

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Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo.

Authors: Pieretti-Vanmarcke, R  Donahoe, PK  Szotek, P  Manganaro, T  Lorenzen, MK  Lorenzen, J  Connolly, DC  Halpern, EF  MacLaughlin, DT 
Citation: Pieretti-Vanmarcke R, etal., Clin Cancer Res. 2006 Mar 1;12(5):1593-8.
RGD ID: 2315652
Pubmed: PMID:16533786   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-05-2108   (Journal Full-text)

PURPOSE: Mullerian inhibiting substance (MIS) is a glycoprotein hormone that causes Mullerian duct regression in male embryos. In short-term experiments, recombinant human MIS (rhMIS) inhibits xenotransplanted human ovarian cancer cell lines that are thought to be of Mullerian origin. Because this highly lethal cancer has a high recurrence rate after conventional chemotherapy, new treatments are warranted. We examined whether rhMIS as a novel, nontoxic, naturally occurring growth inhibitor can be an effective anticancer drug in long-term studies in vivo against allograft tumors that recapitulate human ovarian carcinoma. EXPERIMENTAL DESIGN: Mouse ovarian carcinoma (MOVCAR) cell lines expressing the early region of the SV40 virus, including the large and small T-antigen genes under transcriptional control of a portion of the murine MIS receptor type II (MISRII) gene promoter, were derived from TgMISIIR-TAg transgenic mice. rhMIS was tested against MOVCAR cells in growth inhibition assays in vitro, and in vivo in 6-week-old female nude mice. Tumor growth in animals was measured at weekly intervals for up to 20 weeks. RESULTS: MOVCAR cells and tumors express MISRII by Western blot, immunohistochemical, and Northern blot analyses. rhMIS significantly inhibited MOVCAR cell growth in vitro and in vivo in three separate long-term allotransplantation experiments. CONCLUSIONS: Because rhMIS is an effective anticancer agent in in vitro and in long-term in vivo preclinical experiments against MISRII-positive tumors, we predict that rhMIS can be used safely and effectively to treat human ovarian malignancies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ovarian carcinoma treatmentIDA 2315652 RGD 
ovarian carcinoma treatmentISOAMH (Homo sapiens)2315652; 2315652 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Amh  (anti-Mullerian hormone)

Genes (Mus musculus)
Amh  (anti-Mullerian hormone)

Genes (Homo sapiens)
AMH  (anti-Mullerian hormone)


Additional Information