title: The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.
abstract: We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.
authors: Department of Cancer Research, Berlex Biosciences, Richmond, CA 94804, USA.
authors: Donato
authors: D
authors: Tedesco
authors: Jianhuan
authors: J
authors: Zhang
authors: Lan
authors: L
authors: Trinh
authors: Guita
authors: G
authors: Lalehzadeh
authors: Rene
authors: R
authors: Meisner
authors: Ken D
authors: KD
authors: Yamaguchi
authors: Daniel L
authors: DL
authors: Ruderman
authors: Harald
authors: H
authors: Dinter
authors: Deborah A
authors: DA
authors: Zajchowski
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D015533:Transcriptional Activation; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004317:Doxorubicin; C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes
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