Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells

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dc.contributor.authorDrabsch, Y.
dc.contributor.authorHugo, H.
dc.contributor.authorZhang, R.
dc.contributor.authorDowhan, D.
dc.contributor.authorMiao, Y.
dc.contributor.authorGewirtz, A.
dc.contributor.authorBarry, S.
dc.contributor.authorRamsay, R.
dc.contributor.authorGonda, T.
dc.date.issued2007
dc.descriptionCopyright © 2007 by the National Academy of Sciences
dc.description.abstractMYB (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.
dc.description.statementofresponsibilityYvette Drabsch, Honor Hugo, Rui Zhang, Dennis H. Dowhan, Yu Rebecca Miao, Alan M. Gewirtz, Simon C. Barry, Robert G. Ramsay, and Thomas J. Gonda
dc.identifier.citationProceedings of the National Academy of Sciences of USA, 2007; 104(34):13762-13767
dc.identifier.doi10.1073/pnas.0700104104
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.orcidBarry, S. [0000-0002-0597-7609]
dc.identifier.orcidGonda, T. [0000-0002-8792-3021]
dc.identifier.urihttp://hdl.handle.net/2440/41982
dc.language.isoen
dc.publisherNatl Acad Sciences
dc.source.urihttps://doi.org/10.1073/pnas.0700104104
dc.subjecttranscriptional attenuation
dc.subjectcell cycle
dc.subjectproliferation
dc.subjectantisense
dc.subjectshort hairpin RNA
dc.titleMechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells
dc.typeJournal article
pubs.publication-statusPublished

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