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Adenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter

DC FieldValueLanguage
dc.contributor.author이은직-
dc.date.accessioned2016-02-19T11:12:10Z-
dc.date.available2016-02-19T11:12:10Z-
dc.date.issued2001-
dc.identifier.issn0021-972X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/142625-
dc.description.abstractManagement of Cushing’s disease remains challenging, despite advances in its diagnosis and treatment. Here, we describe a strategy for targeting the expression of toxic genes to ACTH-producing tumor cells using adenoviral vectors. The POMC promoter was used to express either a marker gene (β-galactosidase) or a toxic gene [herpes simplex virus thymidine kinase (TK)]. In ACTH-producing AtT20 cells, infection with recombinant adenoviruses containing the POMC promoter (AdPOMCGal; AdPOMCTK) led to high-level gene expression. Stereotactic injection of AdPOMCGal into the rat pituitary resulted in localized expression of the β-galactosidase transgene in corticotrope cells. Cytotoxicity studies were performed using the TK-containing vectors and treatment with ganciclovir. AdPOMCTK caused greater than 95% cytotoxicity of AtT20 cells at a viral dose (multiplicity of infection, 5 plaque-forming units/cell) that induced minimal toxicity using control viruses. No cellular toxicity was seen using a nonpituitary cell line (T47D breast tumor cells). AtT20 cells transplanted into nude mice induced features of Cushing’s syndrome and were used as an in vivo model of ACTH-producing tumors. Injection of the AdPOMCTK virus caused significant regression of the transplanted AtT20 tumors. These studies suggest that the POMC promoter may provide a useful gene therapy strategy for the adjunctive treatment of pituitary tumors causing ACTH-dependent Cushing’s syndrome.-
dc.description.statementOfResponsibilityopen-
dc.format.extent3400~3409-
dc.relation.isPartOfJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdenoviridae/genetics*-
dc.subject.MESHAdrenocorticotropic Hormone/biosynthesis*-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line-
dc.subject.MESHDNA, Recombinant/administration & dosage-
dc.subject.MESHGanciclovir/administration & dosage-
dc.subject.MESHGene Expression*-
dc.subject.MESHGene Targeting*-
dc.subject.MESHGenetic Therapy-
dc.subject.MESHGenetic Vectors-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHMice, Nude-
dc.subject.MESHNeoplasm Transplantation-
dc.subject.MESHPituitary Neoplasms/metabolism-
dc.subject.MESHPituitary Neoplasms/pathology-
dc.subject.MESHPituitary Neoplasms/therapy*-
dc.subject.MESHPro-Opiomelanocortin/genetics*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHSimplexvirus/enzymology-
dc.subject.MESHThymidine Kinase/genetics-
dc.subject.MESHTransfection-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHbeta-Galactosidase/genetics-
dc.titleAdenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorFred Martinson-
dc.contributor.googleauthorTom Kotlar-
dc.contributor.googleauthorBayar Thimmapaya-
dc.contributor.googleauthorJ. Larry Jameson-
dc.identifier.doi10.1210/jcem.86.7.7726-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03050-
dc.relation.journalcodeJ01318-
dc.identifier.eissn1945-7197-
dc.identifier.pmid11443217-
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/jcem.86.7.7726-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.rights.accessRightsnot free-
dc.citation.volume86-
dc.citation.number7-
dc.citation.startPage3400-
dc.citation.endPage3409-
dc.identifier.bibliographicCitationJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.86(7) : 3400-3409, 2001-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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