Perspectives on c-Myc, Cyclin D1, and their interaction in cancer formation, progression, and response to chemotherapy.
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 TGFalpha, epidermal growth factor receptor, Ras, PI3K/Akt, and NF-kappaB. 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.
Liao
D Joshua
DJ
Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USA. djliao@hi.umn.edu
Thakur
Archana
A
Wu
Jack
J
Biliran
Hector
H
Sarkar
Fazlul H
FH
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000235:genetics*; D018450:Disease Progression; D016259:Genes, myc; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D000970:Antineoplastic Agents; D019938:Cyclin D1