Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-10-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2965668?pdf=render |
| _version_ | 1818486757675499520 |
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| author | J Anthony Graves Kristi Rothermund Tao Wang Wei Qian Bennett Van Houten Edward V Prochownik |
| author_facet | J Anthony Graves Kristi Rothermund Tao Wang Wei Qian Bennett Van Houten Edward V Prochownik |
| author_sort | J Anthony Graves |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-845ac7bd31234c878d64ae44e7c85b3f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T16:27:16Z |
| publishDate | 2010-10-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-845ac7bd31234c878d64ae44e7c85b3f2022-12-22T01:41:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1371710.1371/journal.pone.0013717Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts.J Anthony GravesKristi RothermundTao WangWei QianBennett Van HoutenEdward V ProchownikDeregulation 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.http://europepmc.org/articles/PMC2965668?pdf=render |
| spellingShingle | J Anthony Graves Kristi Rothermund Tao Wang Wei Qian Bennett Van Houten Edward V Prochownik Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. PLoS ONE |
| title | Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. |
| title_full | Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. |
| title_fullStr | Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. |
| title_full_unstemmed | Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. |
| title_short | Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts. |
| title_sort | point mutations in c myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts |
| url | http://europepmc.org/articles/PMC2965668?pdf=render |
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