TY - JOUR
T1 - MicroRNA cluster 221-222 and estrogen receptor α interactions in breast cancer
AU - Di Leva, Gianpiero
AU - Gasparini, Pierluigi
AU - Piovan, Claudia
AU - Ngankeu, Apollinaire
AU - Garofalo, Michela
AU - Taccioli, Cristian
AU - Iorio, Marilena V.
AU - Li, Meng
AU - Volinia, Stefano
AU - Alder, Hansjuerg
AU - Nakamura, Tatsuya
AU - Nuovo, Gerard
AU - Liu, Yunlong
AU - Nephew, Kenneth P.
AU - Croce, Carlo M.
PY - 2010/5
Y1 - 2010/5
N2 - Background: Several lines of evidence have suggested that estrogen receptor α (ERα)-negative breast tumors, which are highly aggressive and nonresponsive to hormonal therapy, arise from ERα-positive precursors through different molecular pathways. Because microRNAs (miRNAs) modulate gene expression, we hypothesized that they may have a role in ER-negative tumor formation. Methods: Gene expression profiles were used to highlight the global changes induced by miRNA modulation of ERα protein. miRNA transfection and luciferase assays enabled us to identify new targets of miRNA 206 (miR-206) and miRNA cluster 221-222 (miR-221-222). Northern blot, luciferase assays, estradiol treatment, and chromatin immunoprecipitation were performed to identify the miR-221-222 transcription unit and the mechanism implicated in its regulation. Results: Different global changes in gene expression were induced by overexpression of miR-221-222 and miR-206 in ER-positive cells. miR-221 and-222 increased proliferation of ERα-positive cells, whereas miR-206 had an inhibitory effect (mean absorbance units [AU]: miR-206: 500 AU, 95% confidence interval [CI]) = 480 to 520; miR-221: 850 AU, 95% CI = 810 to 873; miR-222: 879 AU, 95% CI = 850 to 893; P
AB - Background: Several lines of evidence have suggested that estrogen receptor α (ERα)-negative breast tumors, which are highly aggressive and nonresponsive to hormonal therapy, arise from ERα-positive precursors through different molecular pathways. Because microRNAs (miRNAs) modulate gene expression, we hypothesized that they may have a role in ER-negative tumor formation. Methods: Gene expression profiles were used to highlight the global changes induced by miRNA modulation of ERα protein. miRNA transfection and luciferase assays enabled us to identify new targets of miRNA 206 (miR-206) and miRNA cluster 221-222 (miR-221-222). Northern blot, luciferase assays, estradiol treatment, and chromatin immunoprecipitation were performed to identify the miR-221-222 transcription unit and the mechanism implicated in its regulation. Results: Different global changes in gene expression were induced by overexpression of miR-221-222 and miR-206 in ER-positive cells. miR-221 and-222 increased proliferation of ERα-positive cells, whereas miR-206 had an inhibitory effect (mean absorbance units [AU]: miR-206: 500 AU, 95% confidence interval [CI]) = 480 to 520; miR-221: 850 AU, 95% CI = 810 to 873; miR-222: 879 AU, 95% CI = 850 to 893; P
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U2 - 10.1093/jnci/djq102
DO - 10.1093/jnci/djq102
M3 - Article
C2 - 20388878
AN - SCOPUS:77952921840
VL - 102
SP - 706
EP - 721
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 10
ER -