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Critical Reviews™ in Oncogenesis

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v13.i2.10
pages 93-158

Perspectives on c-Myc, Cyclin D1, and Their Interaction in Cancer Formation, Progression, and Response to Chemotherapy

D. Joshua Liao
Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USA
Archana Thakur
Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, 740 HWCRC, 4100 John R, Detroit, MI 48201, USA
Jack Wu
Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USA
Hector Biliran
Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, 740 HWCRC, 4100 John R, Detroit, MI 48201, USA
Fazlul H. Sarkar
Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, 740 HWCRC, 4100 John R, Detroit, MI 48201, USA

ABSTRACT

C-myc is an oncogene that functions both in the stimulation of cell proliferation and in and apoptosis. C-myc elicits its oncogenic activity by causing immortalization, and to a lesser extent the transformation of cells, in addition to several other mechanisms. C-myc may also enhance or reduce the sensitivity of cancer cells to chemotherapy, but how this dual function is controlled is largely unclear. Cyclin D1 (D1) is another oncogene that drives cell cycle progression; it acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery, though it may also promote apoptosis. C-Myc collaborates with TGFα, epidermal growth factor receptor, Ras, PI3K/Akt, and NF-κB. in part via coordination in regulation of D1 expression, because D1 is a common downstream effector of these growth pathways. Coordination of c-Myc with D1 or its upstream activators not only accelerates tumor formation, but also may drive tumor progression to a more aggressive phenotype. Because c-Myc may effect immortalization while D1 or its upstream activators elicit transformation, targeting c-myc and D1 may be a good strategy for cancer prevention. Moreover, since D1 imposes chemoresistance on cancer cells, targeting D1 may also be a good strategy for cancer chemotherapy, whereas practicioners should be cautious to downregulate c-myc for chemotherapy, since c-Myc may elicit apoptosis.