Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

Bièche, Ivan; Girault, Igor; Urbain, Estelle; Tozlu, Sengül; Lidereau, Rosette

doi:10.1186/bcr784

Cited by 96 publications

(92 citation statements)

References 28 publications

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“…In addition, to CYP2B6 and CA12 that are already known to be ERa-related in breast cancer (Gruvberger et al 2001, Bieche et al 2004b, we identified a third gene (IL6ST) that perfectly predicted ERa status in our breast tumor series (AUC-ROC, 1.000). IL6ST encodes gp130, the subunit shared by the different receptors of IL-6 family cytokines, including interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 (Kishimoto et al 1994).…”

Section: Discussionmentioning

confidence: 78%

“…The only gene showing significantly different expression (PZ0.024) between patients, who relapsed (nZ12) and those, who did not relapse (nZ12) was NAT1. It is noteworthy that, in a previous study of 125 ERa-positive postmenopausal breast cancer patients, we identified NAT1 and CGA (also identified in the present study) as independent predictors of the response to tamoxifen (Bieche et al 2001b(Bieche et al , 2004b.…”

Section: Discussionmentioning

confidence: 87%

“…Several new genes, such as GATA3, TFF3, MYB, IGFBP4, IGFBP5, STC2, KRT18, HPN/HEPSIN, FOXA1, XBP1, SLC39A6/LIV-1 and CA12 M, were recently identified by microarray studies (Gruvberger et al 2001, Bertucci et al 2002, van't Veer et al 2002. For our part, we have previously identified CGA, NAT1 Endocrine-Related Cancer (2006) 13 1109-1120 www.endocrinology-journals.org and CYP2B6 as candidate ERa-responsive genes in human breast cancer (Bieche et al 2001b(Bieche et al , 2004b.…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach

Tozlu

Girault²,

Vacher³

et al. 2006

Endocr Relat Cancer

215

162

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The estrogen receptor alpha (ERa) plays a critical role in the pathogenesis and clinical behavior of breast cancer. To obtain further insights into the molecular basis of estrogen-dependent forms of this malignancy, we used real-time quantitative reverse transcription (RT)-PCR to compare the mRNA expression of 560 selected genes in ERa-positive and ERa-negative breast tumors. Fifty-one (9.1%) of the 560 genes were significantly upregulated in ERa-positive breast tumors compared with ERa-negative breast tumors. In addition to well-known ERa-induced genes (PGR, TFF1/PS2, BCL2, ERBB4, CCND1, etc.) and genes recently identified by cDNA microarray-based approaches (GATA3, TFF3, MYB, STC2, HPN/HEPSIN, FOXA1, XBP1, SLC39A6/LIV-1, etc.), an appreciable number of novel genes were identified, many of, which were weakly expressed. This validates the use of large-scale real-time RT-PCR as a method complementary to cDNA microarrays for molecular tumor profiling. Most of the new genes identified here encoded secreted proteins (SEMA3B and CLU), growth factors (BDNF, FGF2 and EGF), growth factor receptors (IL6ST, PTPRT, RET, VEGFR1 and FGFR2) or metabolic enzymes (CYP2B6, CA12, ACADSB, NAT1, LRBA, SLC7A2 and SULT2B1). Importantly, we also identified a large number of genes encoding proteins with either pro-apoptotic (PUMA, NOXA and TATP73) or anti-apoptotic properties (BCL2, DNTP73 and TRAILR3). Surprisingly, only a small proportion of the 51 genes identified in breast tumor biopsy specimens were confirmed to be ERa-regulated and/or E2-regulated in vitro (cultured cell lines). Therefore, this study identified a limited number of genes and signaling pathways, which better delineate the role of ERa in breast cancer. Some of the genes identified here could be useful for diagnosis or for predicting endocrine responsiveness, and could form the basis for novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach

Tozlu

Girault²,

Vacher³

et al. 2006

Endocr Relat Cancer

215

162

View full text Add to dashboard Cite

show abstract

“…Several studies have shown higher mRNA and protein expression of NAT1 in ER-positive breast cancer compared with the expression in ER-negative disease (Perou et al 2000, Adam et al 2003, Tozlu et al 2006, Wakefield et al 2008. Moreover, it was reported that high expression of NAT1 was correlated with better outcome in ER-positive breast cancer (Bieche et al 2004, Dolled-Filhart et al 2006. Our results demonstrated that NAT1 mRNA expression was much higher in ER high Ki67 low tumors than in ER Gene expressions of miR-1290 putative targets in T47D and MCF-7 cells transfected with miR-1290.…”

Section: Discussionmentioning

confidence: 99%

miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer

Endo

Toyama

Takahashi

et al. 2012

Endocrine-Related Cancer

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Recent analyses have identified heterogeneity in estrogen receptor a (ERa)-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis, are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. In this study, expression profiles of microRNAs (miRNAs) (let-7a, miR-15a, miR-26a, miR-34a, miR-193b, and miR-342-3p). We picked up 11 genes that were potential target genes of the selected miRNAs and that were differentially expressed in ER high Ki67 low tumors and ER low Ki67 high tumors. Protein expression patterns of the selected target genes were analyzed in 256 ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its putative targets, BCL2, FOXA1, MAPT, and NAT1, were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased expression of NAT1 and FOXA1. Our results suggest that miR-1290 and its potential targets might be associated with characteristics of ER-positive breast cancer.

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“…Third, the clearance of nicotine and cotinine was significantly higher during pregnancy (Dempsey et al, 2002). In addition to these findings, a recent in vitro study demonstrated that the expression level of CYP2A6 mRNA was significantly higher in estrogen receptor ␣ (ER␣; NR3A1)-positive breast tumors than in ER␣-negative breast tumors (Bièche et al, 2004). This background prompted us to investigate the roles of estrogen in regulating CYP2A6.…”

mentioning

confidence: 97%

Human CYP2A6 Is Induced by Estrogen via Estrogen Receptor

Higashi

Fukami²,

Itoh³

et al. 2007

Drug Metab Dispos

124

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ABSTRACT:Human CYP2A6, which is predominantly expressed in liver, is a key enzyme responsible for the metabolism of nicotine, coumarin, and some pharmaceutical drugs. CYP2A6 is also expressed in sex steroid-responsive tissues such as breast, ovary, uterus, testis, and adrenal grand. In this study, we examined the regulation of CYP2A6 gene by estrogen. Reverse transcription-polymerase chain reaction (RT-PCR) assays revealed that CYP2A6 mRNA was induced by estradiol in estrogen receptor (ER)-positive MCF-7 (2.9-fold) and HepG2 (1.3-fold) cells, but not in ER-negative MDA-MB-435 cells. Real-time RT-PCR assays revealed the CYP2A6 induction by estradiol in human hepatocytes (1.2-to 1.5-fold). Computer-assisted homology search identified a putative estrogen response element (ERE) at ؊2436 on the CYP2A6 gene. Electrophoretic mobility shift assays demonstrated specific binding of ER␣ to this element. Luciferase assays using MCF-7 cells revealed that the transcriptional activity of the CYP2A6 promoter was significantly activated by estradiol in an ER␣-dependent manner, in which ERE was responsible for the activation. Chromatin immunoprecipitation assays verified the in vivo association of ER␣ with the ERE on the CYP2A6 gene. Immunohistochemical analyses using human endometrial tissues indicated that the CYP2A6 protein level in glandular cells was significantly higher in the proliferative phase than in the secretory phase, concomitant with local estrogen secretion during the menstrual cycle. These findings clearly demonstrated that CYP2A6 is directly induced by estrogen in an ER␣-dependent manner, implying a biological role of CYP2A6 in estrogen-responsive tissues. Furthermore, this mechanism can also explain clinical aspects of increased nicotine metabolism under estrogen-rich environments.

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Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

Cited by 96 publications

References 28 publications

Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach

Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach

miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer

Human CYP2A6 Is Induced by Estrogen via Estrogen Receptor

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