title: Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells.
abstract: MYB (the human ortholog of c-myb) is expressed in a high proportion of human breast tumors, and that expression correlates strongly with estrogen receptor (ER) positivity. This may reflect the fact that MYB is a target of estrogen/ER signaling. Because in many cases MYB expression appears to be regulated by transcriptional attenuation or pausing in the first intron, we first investigated whether this mechanism was involved in estrogen/ER modulation of MYB. We found that this was the case and that estrogen acted directly to relieve attenuation due to sequences within the first intron, specifically, a region potentially capable of forming a stem-loop structure in the transcript and an adjacent poly(dT) tract. Secondly, given the involvement of MYB in hematopoietic and colon tumors, we also asked whether MYB was required for the proliferation of breast cancer cells. We found that proliferation of ER(+) but not ER(-) breast cancer cell lines was inhibited when MYB expression was suppressed by using either antisense oligonucleotides or RNA interference. Our results show that MYB is an effector of estrogen/ER signaling and provide demonstration of a functional role of MYB in breast cancer.
authors: University of Queensland Diamantina Institute for Cancer, Immunology, and Metabolic Medicine, Brisbane, Queensland 4102, Australia.
authors: Yvette
authors: Y
authors: Drabsch
authors: Honor
authors: H
authors: Hugo
authors: Rui
authors: R
authors: Zhang
authors: Dennis H
authors: DH
authors: Dowhan
authors: Yu Rebecca
authors: YR
authors: Miao
authors: Alan M
authors: AM
authors: Gewirtz
authors: Simon C
authors: SC
authors: Barry
authors: Robert G
authors: RG
authors: Ramsay
authors: Thomas J
authors: TJ
authors: Gonda
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D004967:Estrogens; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D011960:Receptors, Estrogen
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