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.

Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines

“…The contradiction between the above findings may be explained in view of previous studies suggesting that the effect of a single gene may differ according to the genetic and cellular context. For example, c-MYC can induce both cell proliferation and apoptosis (Evan et al, 1992;Jain et al, 2002;Pelengaris et al, 2002). Another example was given by Serrano et al (1997), who showed that the oncogene ras, known for its ability to transform immortal rodent cells to a tumourigenic state, can provoke premature cell senescence in primary human and rodent cells.…”

Application of Stem Cells in Targeted Therapy of Breast Cancer: A Systematic Review

“…Therefore, targeting Wnt/β-catenin pathway that is responsible for self-renewal can be a potential therapeutics strategy (Woodward et al, 2007). Although mutation of β-catenin may not commonly occurred in human breast cancers, various studies showed the role of Wnt signaling pathway in pathogenesis of breast cancer (Lin et al, 2000;Jain et al, 2002;Wong et al, 2002;Klopocki et al, 2004) suggesting a link between Wnt signaling and DNA damage response in epithelial cells (Ayyanan et al, 2006).…”

Epigenesis and Dynamic Similarity in Two Regulatory Networks in Pseudomonas Aeruginosa

“…Weinstein (2000) wrote that even if the development of microarray methods and proteomics expands our ability to assess complex profiles of gene expression in cancer cells, these methods do not provide the dynamic view of the actual circuitry of these cells. Recently, however, direct experimental evidence of an epigenetic mechanism has been reported: the MYC oncogene is frequently overexpressed in cancer cells and its brief inactivation in an osteogenic sarcoma cell line appeared to cause epigenetic changes that rendered the cells insensitive to MYCinduced tumorigenesis (Jain et al, 2002).…”