Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer.
Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer.
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DOI：
10.1002/cncr.24103
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发表时间：
2009-02-15
期刊：
影响因子：
6.2
通讯作者：
Shapiro, Charles L.
中科院分区：
文献类型：
--
作者：
Guler, Gulnur;Huebner, Kay;Himmetoglu, Cigdem;Jimenez, Rafael E.;Costinean, Stefan;Volinia, Stefano;Pilarski, Robert T.;Hayran, Mutlu;Shapiro, Charles L.
关键词：
脆性基因座FRA 3B和FRA 16 D编码的肿瘤抑制因子Fhit和Wwox蛋白的表达在乳腺癌中一致丢失。本研究探讨了Fhit、Wwox、转录因子AP 2 α和AP 2 γ、细胞角蛋白5/6（CK 5/6）、表皮生长因子受体（EGFR）、雌激素受体（ER）、孕激素受体（PR）、HER 2与乳腺癌表型的相关性。从837个乳腺癌块构建的组织微阵列进行免疫染色。在>10%的肿瘤细胞中表达被认为是细胞质CK 5/6、膜EGFR、核AP 2 α和AP 2 γ阳性。根据染色强度对细胞质Fhit和Wwox染色进行评分。肿瘤ER、PR和HER 2状态均来自记录。通过单因素和多因素统计方法评估免疫组化标记物与肿瘤亚型之间的相关性。三阴性肿瘤中EGFR、CK 5/6（p<0.001）和AP 2 γ（p = 0.003）的表达更频繁，Fhit和Wwox的丢失更频繁（p<0.001），Fhit、Wwox与EGFR、ER、PR表达呈负相关（p<0.001）。Fhit表达减少在HER 2和AP 2 γ阳性病例中更常见（p<0.001，p=0.002）。Fhit和Wwox之间存在直接相关性（p<0.001），AP 2 α和γ之间存在临界正相关性（p=0.054）。结果提示，Fhit、Wwox和核内AP 2 γ表达降低在乳腺癌基底细胞样分化的发病机制中起一定作用。脆性位点基因表达的改变发生在大多数这些癌症中，并可能导致DNA修复缺陷，如在BRCA 1缺陷型癌症中观察到的。因此，DNA损伤反应检查点蛋白可能是治疗的靶点。
Expression of Fhit and Wwox proteins, tumor suppressors encoded by fragile loci FRA3B and FRA16D, are concordantly lost in breast cancers. The current study examined correlations among Fhit, Wwox, transcription factors AP2α and AP2γ, cytokeratins 5/6 (CK5/6), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), HER2 and their associations with breast cancer phenotypes. Tissue microarrays constructed from 837 breast cancer blocks were immunostained. Expression in >10% of tumor cells was considered positive for cytoplasmic CK5/6, membranous EGFR, nuclear AP2α and AP2γ. Cytoplasmic Fhit and Wwox staining was scored according to staining intensity. ER, PR and HER2 status of tumors was from records. Correlations among immunohistochemical markers and tumor subtypes were assessed by univariate and multivariate statistical methods. Triple negative tumors showed more frequent expression of EGFR, CK5/6 (p<0.001) and AP2γ (p = 0.003) and more frequent loss of Fhit and Wwox (p<0.001), with inverse correlation between Fhit, Wwox and EGFR, ER, PR expression (p<0.001). Reduced Fhit expression was more common in HER2 and AP2γ positive cases (p<0.001, p=0.002). There was direct correlation between Fhit and Wwox (p<0.001) and a borderline positive relation between AP2α and γ (p=0.054). Results suggest that reduced Fhit, Wwox and nuclear AP2γ expression have roles in pathogenesis of basal-like differentiation in breast cancer. Alteration of expression of fragile site genes occurs in most of these cancers and may contribute to defects in DNA repair, as observed in BRCA1-deficient cancers. Thus DNA damage response checkpoint proteins could be targets for treatment.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
11.2
作者：
Aqeilan, RI;Donati, V;Croce, CM
通讯作者：
Croce, CM
影响因子：
11.2
作者：
Ishii, Hideshi;Mimori, Koshi;Huebner, Kay
通讯作者：
Huebner, Kay
影响因子：
11.5
作者：
Guler, Gulnur;Iliopoulos, Dimitrios;Huebner, Kay
通讯作者：
Huebner, Kay
DOI：
10.1073/pnas.0711613105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Liu, Suling;Ginestier, Christophe;Wicha, Max S.
通讯作者：
Wicha, Max S.