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A polymorphism in the TC21 promoter associates with an unfavorable tamoxifen treatment outcome in breast cancerRokavec, Matjaž ...Tamoxifen therapy is a standard in the treatment of estrogen receptor (ER)-positive breast cancer; however, its efficacy varies widely among patients. In addition to interpatient differences in the ... tamoxifen-metabolizing capacity, there is growing evidence that crosstalk between ER and growth factor signaling contributes to tamoxifen resistance. Wefocused on TC21, a member of the Ras superfamily, to investigate the influence of the TC21 -582C>T promoter polymorphism on TC21 expression and treatment outcome. Immunohistochemical analyses of breast tumors revealed a higher TC21 expression in ER-negative compared with ER-positive tumors. Expression in ER-positive tumors was higher in carriers of the T allele in anallele dose-dependent manner. Quantitative real-time PCR analyses showed that TC21 mRNA expression is decreased after transfection of ERalpha in ER-negative breast cancer cells MDA-MB-231, UACC893, and BT-20. In MCF7 ER-positive cells, TC21 expression decreased with 17beta-estradiol treatment and increased after treatment with tamoxifen metabolites, 4-OH-tamoxifen, or endoxifen. In patients treated with adjuvant mono tamoxifen, high cytoplasmic TC21 tumor expression or the carriership of the -582T allele conferred increased recurrence rates šn=45: hazard ratio (HR), 3.06; 95% confidence interval (95% CI), 1.16-8.05; n=206: HR, 1.79; 95% CI, 1.08-3.00, respectivelyđ. A combined analysis with the data of the known tamoxifen predictor CYP2D6 showed an improvement of outcome prediction compared with CYP2D6 or TC21 genotype status alone (per mutated gene HR, 2.35; 95% CI, 1.34-4.14). Our functional and patient-based results suggest that the TC21 -582C>T polymorphism improves prediction of tamoxifen treatment outcome in breast cancer.Source: Cancer research. - ISSN 0008-5472 (Letn. 68, št. 23, 2008, str. 9799-9808)Type of material - article, component partPublish date - 2008Language - englishCOBISS.SI-ID - 26558169
Author
Rokavec, Matjaž |
Schroth, Werner |
Amaral, Sandra M.C. |
Glavač, Damjan
Topics
Adult |
Aged |
Aged, 80 And Over |
Alleles |
Antineoplastic Agents, Hormonal |
Pharmacology |
Breast Neoplasms |
Drug Therapy |
Genetics |
Metabolism |
Chemotherapy, Adjuvant |
Cytochrome P-450 Cyp2d6 |
Genetics |
Dna, Neoplasm |
Metabolism |
Electrophoresis |
Genotype |
Immunohistochemistry |
Membrane Proteins |
Biosynthesis |
Genetics |
Metabolism |
Rna, Messenger |
Biosynthesis |
Genetics |
Tamoxifen |
Pharmacology |
RNA, prenašalna |
Kemoterapija pomožna |
DNA novotvorbe |
Starostniki |
Starost 80 in več |
Imunohistokemija |
Odrasli |
Antineoplastiki hormonski |
Dojka, novotvorbe |
Membranske beljakovine |
Tamoksifen |
Genotip |
Elektroforeza |
Aleli |
Citokrom P-450 CYP2D6
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Rokavec, Matjaž | ![]() |
Schroth, Werner | ![]() |
Amaral, Sandra M.C. | ![]() |
Glavač, Damjan | 09275 |
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