Low-molecular-weight cyclin E: the missing link between biology and clinical outcome.
Cyclin E, a key mediator of transition during the G1/S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability.
Akli
Said
S
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Keyomarsi
Khandan
K
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D002455:Cell Division; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000494:pharmacology; D051379:Mice; D011379:Prognosis; D020033:Protein Isoforms; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; C493957:Cdkn1a protein, mouse; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004965:Estrogen Antagonists; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53