Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. Cancer Res 2011 Dec 15;71(24):7513-24
Date
11/01/2011Pubmed ID
22037875Pubmed Central ID
PMC3242818DOI
10.1158/0008-5472.CAN-11-1783Scopus ID
2-s2.0-84255170423 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.
Author List
Zhang Q, Sakamoto K, Liu C, Triplett AA, Lin WC, Rui H, Wagner KUMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Cyclin D1
Cyclin D3
Disease Progression
Female
Humans
Immunohistochemistry
Mammary Neoplasms, Animal
Mice
Mice, Knockout
Mice, Transgenic
NIH 3T3 Cells
RNA Interference
Receptor, ErbB-2
