Sustained loss of a neoplastic phenotype by brief inactivation of MYC.
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.
Jain
Meenakshi
M
Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA 94305-5151, USA.
Arvanitis
Constadina
C
Chu
Kenneth
K
Dewey
William
W
Leonhardt
Edith
E
Trinh
Maxine
M
Sundberg
Christopher D
CD
Bishop
J Michael
JM
Felsher
Dean W
DW
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
D000970:Antineoplastic Agents; D004318:Doxycycline