Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function.
The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2 significantly influences cell cycle, apoptosis, cytoskeleton, and membrane trafficking pathways. J. Mol. Biol. 346 (2005) 83-89]. Its tumor suppression mechanism, however, remains unclear. In this paper, we demonstrate that DBC2 suppresses breast cancer proliferation through down-regulation of Cyclin D1 (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the expression of CCNE1 exhibited the same protective effect. Our results indicate that the down-regulation of CCND1 is an essential step for DBC2's growth suppression of cancer cells. We believe that this discovery contributes to a better understanding of DBC2's tumor suppressor function.
Yoshihara
Takashi
T
Department of Biological Sciences, Fordham University, 441 E Fordham Road, Larkin Hall, Bronx, NY 10458, USA.
Collado
Denise
D
Hamaguchi
Masaaki
M
D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism*; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D056741:Cyclin D; D016213:Cyclins; C497336:RHOBTB2 protein, human; D025521:Tumor Suppressor Proteins; D019204:GTP-Binding Proteins