Article

Reviewing once more the c-myc and Ras collaboration Converging at the cyclin D1-CDK4 complex and challenging basic concepts of cancer biology

Department of Stem Cell and Regenerative Medicine, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 01/2011; 10(1):57-67. DOI: 10.4161/cc.10.1.14449
Source: PubMed

ABSTRACT

The c-myc is a proto-oncogene that manifests aberrant expression at high frequencies in most types of human cancer. C-myc gene amplifications are often observed in various cancers as well. Ample studies have also proved that c-myc has a potent oncogenicity, which can be further enhanced by collaborations with other oncogenes such as Bcl-2 and activated Ras. Studies on the collaborations of c-myc with Ras or other genes in oncogenicity have established several basic concepts and have disclosed their underlying mechanisms of tumor biology, including "immortalization" and "transformation". In many cases, these collaborations may converge at the cyclin D1-CDK4 complex. In the meantime, however, many results from studies on the c-myc, Ras and cyclin D1-CDK4 also challenge these basic concepts of tumor biology and suggest to us that the immortalized status of cells should be emphasized. Stricter criteria and definitions for a malignantly transformed status and a benign status of cells in culture also need to be established to facilitate our study of the mechanisms for tumor formation and to better link up in vitro data with animal results and eventually with human cancer pathology.

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    • "Thus, it is possible that attenuation of c-Myc protein in RCC cells by PPARα antagonism was through increased let-7c resulting in decreased stability of c-Myc. The cyclin D1/CDK4 complex promotes cell cycle progression through phosphorylation of its substrate including pRb (reviewed in [42]). Attenuation of c-Myc represses cyclin D1/CDK4 expression and activity at G1/S transition [43], [44]. "
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