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Adenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter
DC Field | Value | Language |
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dc.contributor.author | 이은직 | - |
dc.date.accessioned | 2016-02-19T11:12:10Z | - |
dc.date.available | 2016-02-19T11:12:10Z | - |
dc.date.issued | 2001 | - |
dc.identifier.issn | 0021-972X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/142625 | - |
dc.description.abstract | Management 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.statementOfResponsibility | open | - |
dc.format.extent | 3400~3409 | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adenoviridae/genetics* | - |
dc.subject.MESH | Adrenocorticotropic Hormone/biosynthesis* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | DNA, Recombinant/administration & dosage | - |
dc.subject.MESH | Ganciclovir/administration & dosage | - |
dc.subject.MESH | Gene Expression* | - |
dc.subject.MESH | Gene Targeting* | - |
dc.subject.MESH | Genetic Therapy | - |
dc.subject.MESH | Genetic Vectors | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Neoplasm Transplantation | - |
dc.subject.MESH | Pituitary Neoplasms/metabolism | - |
dc.subject.MESH | Pituitary Neoplasms/pathology | - |
dc.subject.MESH | Pituitary Neoplasms/therapy* | - |
dc.subject.MESH | Pro-Opiomelanocortin/genetics* | - |
dc.subject.MESH | Promoter Regions, Genetic | - |
dc.subject.MESH | Simplexvirus/enzymology | - |
dc.subject.MESH | Thymidine Kinase/genetics | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.subject.MESH | beta-Galactosidase/genetics | - |
dc.title | Adenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Eun Jig Lee | - |
dc.contributor.googleauthor | Fred Martinson | - |
dc.contributor.googleauthor | Tom Kotlar | - |
dc.contributor.googleauthor | Bayar Thimmapaya | - |
dc.contributor.googleauthor | J. Larry Jameson | - |
dc.identifier.doi | 10.1210/jcem.86.7.7726 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03050 | - |
dc.relation.journalcode | J01318 | - |
dc.identifier.eissn | 1945-7197 | - |
dc.identifier.pmid | 11443217 | - |
dc.identifier.url | http://press.endocrine.org/doi/abs/10.1210/jcem.86.7.7726 | - |
dc.contributor.alternativeName | Lee, Eun Jig | - |
dc.contributor.affiliatedAuthor | Lee, Eun Jig | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 86 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 3400 | - |
dc.citation.endPage | 3409 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.86(7) : 3400-3409, 2001 | - |
dc.identifier.rimsid | 31148 | - |
dc.type.rims | ART | - |
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