原创力文档aromatase inhibitors, estrogens and musculoskeletal pain estrogen-dependent t-cell leukemia 1a (tcl1a) gene-mediated regulation of cytokine expression芳香化酶抑制剂,雌激素和肌肉骨骼疼痛estrogen-dependent t细胞白血病1(tcl1a)gene-mediated调节细胞因子表达.pdfVIP
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aromatase inhibitors, estrogens and musculoskeletal pain estrogen-dependent t-cell leukemia 1a (tcl1a) gene-mediated regulation of cytokine expression芳香化酶抑制剂,雌激素和肌肉骨骼疼痛estrogen-dependent t细胞白血病1(tcl1a)gene-mediated调节细胞因子表达
Liu et al. Breast Cancer Research 2012, 14:R41
/content/14/2/R41
RESEARCH ARTICLE Open Access
Aromatase inhibitors, estrogens and
musculoskeletal pain: estrogen-dependent T-cell
leukemia 1A (TCL1A) gene-mediated regulation of
cytokine expression
1 1 2 3 4 5
Mohan Liu , Liewei Wang , Tim Bongartz , John R Hawse , Svetomir N Markovic , Daniel J Schaid ,
6 6 6 6 7 4
Taisei Mushiroda , Michiaki Kubo , Yusuke Nakamura , Naoyuki Kamatani , Paul E Goss , James N Ingle and
Richard M Weinshilboum1*
Abstract
Introduction: Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of
breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an
estrogen response element near the 3’ end of the T-cell leukemia 1A (TCL1A) gene - that were associated with
musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent,
SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce
IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine
expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects.
Methods: The functional genomic experiments performed included determinations of TCL1A, cytokine and
cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that
had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene
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