Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts

Graves, JA and Rothermund, K and Wang, T and Qian, W and van Houten, B and Prochownik, EV (2010) Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. PLoS ONE, 5 (10).

Published Version
Available under License : See the attached license file.

Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


Deregulation of c-Myc (Myc) occurs in many cancers. In addition to transforming various cell types, Myc also influences additional transformation-associated cellular phenotypes including proliferation, survival, genomic instability, reactive oxygen species production, and metabolism. Although Myc is wild type in most cancers (wtMyc), it occasionally acquires point mutations in certain lymphomas. Some of these mutations confer a survival advantage despite partially attenuating proliferation and transformation. Here, we have evaluated four naturally-occurring or synthetic point mutations of Myc for their ability to affect these phenotypes, as well as to promote genomic instability, to generate reactive oxygen species and to up-regulate aerobic glycolysis and oxidative phosphorylation. Our findings indicate that many of these phenotypes are genetically and functionally independent of one another and are not necessary for transformation. Specifically, the higher rate of glucose metabolism known to be associated with wtMyc deregulation was found to be independent of transformation. One mutation (Q131R) was greatly impaired for nearly all of the studied Myc phenotypes, yet was able to retain some ability to transform. These findings indicate that, while the Myc phenotypes examined here make additive contributions to transformation, none, with the possible exception of increased reliance on extracellular glutamine for survival, are necessary for achieving this state. © 2010 Graves et al.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Graves, JA
Rothermund, K
Wang, T
Qian, Wweq5@pitt.eduWEQ5
van Houten, Bbev15@pitt.eduBEV15
Prochownik, EVevp4@pitt.eduEVP4
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 17 November 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 10
DOI or Unique Handle: 10.1371/journal.pone.0013717
Refereed: Yes
MeSH Headings: Amino Acid Sequence; Animals; Apoptosis--genetics; Cell Proliferation; Cell Transformation, Neoplastic--genetics; Fibroblasts--metabolism; Genes, myc; Genomic Instability; Humans; Molecular Sequence Data; Neoplasms, Experimental--genetics; Neoplasms, Experimental--metabolism; Oxidative Phosphorylation; Phenotype; Point Mutation; Rats
Other ID: NLM PMC2965668
PubMed Central ID: PMC2965668
PubMed ID: 21060841
Date Deposited: 22 Aug 2012 21:03
Last Modified: 02 Feb 2019 13:58


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item