title: Sustained loss of a neoplastic phenotype by brief inactivation of MYC.
abstract: Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model for MYC-induced tumorigenesis to demonstrate that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes. Subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. Thus, brief MYC inactivation appears to cause epigenetic changes in tumor cells that render them insensitive to MYC-induced tumorigenesis. These results raise the possibility that transient inactivation of MYC may be an effective therapy for certain cancers.
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jain
authors.forename: Constadina
authors.initials: C
authors.lastname: Arvanitis
authors.forename: Kenneth
authors.initials: K
authors.lastname: Chu
authors.forename: William
authors.initials: W
authors.lastname: Dewey
authors.forename: Edith
authors.initials: E
authors.lastname: Leonhardt
authors.forename: Maxine
authors.initials: M
authors.lastname: Trinh
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sundberg
authors.forename: J Michael
authors.initials: JM
authors.lastname: Bishop
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing; D016259:Genes, myc; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010011:Osteocytes / Q000166:cytology; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004318:Doxycycline