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.
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Said
S
Akli
Khandan
K
Keyomarsi
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