title: Novel approaches for chemosensitization of breast cancer cells: the E1A story.
abstract: The adenoviral E1A-mediated sensitization to a variety of anti-cancer drug-induced apoptosis is a well-established phenomenon on different types of cell systems. However, the mechanisms underlying E1A-mediated chemosensitization are still not fully understood. Recent studies demonstrate that E1A-mediated sensitization to drug-induced apoptosis can occur via multiple pathways; some of which depend on the expression of functional p53 and/or p19ARF proteins, while some are not. In human breast cancer cells with Her-2/neu overexpression, which usually are more resistance to anti-cancer drugs than cells without Her-2/ neu overexpression, may be sensitized through E1A-mediated downregulation of Her-2/neu. Alternatively, E1A can induce sensitization to anticancer drugs in cancer cells or normal diploid fibroblast cells through upregulating the expression of caspase proenzymes, or downregulating the activity of a critical survival factor Akt and/or upregulating the activities of a pro-apoptotic kinase p38 and a protein phosphatase PP2A, etc. This review summarizes these progresses and proposes a plausible feed-forward model for E1A-mediated chemosensitization in human breast cancer cells.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liao
authors.forename: Dihua
authors.initials: D
authors.lastname: Yu
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases