The combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors.
The combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors.
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DOI：
10.1186/bcr1851
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Begon DY
中科院分区：
文献类型：
--
作者：
Allouche A;Nolens G;Tancredi A;Delacroix L;Mardaga J;Fridman V;Winkler R;Boniver J;Delvenne P;Begon DY
在大约20%的人类乳腺肿瘤中观察到ERBB2癌基因的过表达，这是与基因扩增相关的转录率增加的结果。一些研究表明，在乳腺癌细胞系中，激活蛋白2 （AP-2）转录因子与ERBB2基因表达之间存在联系。此外，阴阳1 （YY1）转录因子在体外已被证明可以刺激ERBB2启动子上AP-2的转录活性。在本报告中，我们研究了乳腺癌组织标本和乳腺癌细胞系中ERBB2、AP-2α和YY1之间的关系。用免疫组化方法分析55例原发性乳腺肿瘤的ERBB2、AP-2α和YY1蛋白水平。荧光原位杂交检测ERBB2基因扩增状态。相关性采用χ2检验，p值小于0.05。采用小干扰RNA （small interfering RNA, siRNA）转染BT-474乳腺癌细胞系，实时逆转录聚合酶链反应和Western blotting分析AP-2α和YY1对ERBB2基因表达的功能作用。肿瘤组织中ERBB2与AP-2α水平有统计学意义（p < 0.01）。此外，ERBB2蛋白水平与AP-2α和YY1联合高表达之间存在相关性（p < 0.02）， AP-2α和YY1表达之间存在相关性（p < 0.001）。此外，AP-2α和YY1蛋白水平与肿瘤中ERBB2基因扩增状态呈负相关（p < 0.01）。在BT-474乳腺癌细胞系中转染靶向AP-2α和AP-2γ mRNA的sirna可在mRNA和蛋白水平上抑制内源性ERBB2基因的表达。此外，针对YY1转录物的siRNA的额外转染进一步降低了ERBB2蛋白水平，这表明AP-2和YY1转录因子协同刺激ERBB2基因的转录。本研究强调了AP-2α和YY1转录因子在乳腺肿瘤中ERBB2癌基因过表达中的作用。我们的研究结果还表明，ERBB2的高表达可能是由于基因扩增或转录因子水平的增加。
Overexpression of the ERBB2 oncogene is observed in about 20% of human breast tumors and is the consequence of increased transcription rates frequently associated with gene amplification. Several studies have shown a link between activator protein 2 (AP-2) transcription factors and ERBB2 gene expression in breast cancer cell lines. Moreover, the Yin Yang 1 (YY1) transcription factor has been shown to stimulate AP-2 transcriptional activity on the ERBB2 promoter in vitro. In this report, we examined the relationships between ERBB2, AP-2α, and YY1 both in breast cancer tissue specimens and in a mammary cancer cell line. ERBB2, AP-2α, and YY1 protein levels were analyzed by immunohistochemistry in a panel of 55 primary breast tumors. ERBB2 gene amplification status was determined by fluorescent in situ hybridization. Correlations were evaluated by a χ2 test at a p value of less than 0.05. The functional role of AP-2α and YY1 on ERBB2 gene expression was analyzed by small interfering RNA (siRNA) transfection in the BT-474 mammary cancer cell line followed by real-time reverse transcription-polymerase chain reaction and Western blotting. We observed a statistically significant correlation between ERBB2 and AP-2α levels in the tumors (p < 0.01). Moreover, associations were found between ERBB2 protein level and the combined high expression of AP-2α and YY1 (p < 0.02) as well as between the expression of AP-2α and YY1 (p < 0.001). Furthermore, the levels of both AP-2α and YY1 proteins were inversely correlated to ERBB2 gene amplification status in the tumors (p < 0.01). Transfection of siRNAs targeting AP-2α and AP-2γ mRNAs in the BT-474 breast cancer cell line repressed the expression of the endogenous ERBB2 gene at both the mRNA and protein levels. Moreover, the additional transfection of an siRNA directed against the YY1 transcript further reduced the ERBB2 protein level, suggesting that AP-2 and YY1 transcription factors cooperate to stimulate the transcription of the ERBB2 gene. This study highlights the role of both AP-2α and YY1 transcription factors in ERBB2 oncogene overexpression in breast tumors. Our results also suggest that high ERBB2 expression may result either from gene amplification or from increased transcription factor levels.
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影响因子：
4.8
作者：
Begon, DY;Delacroix, L;Winkler, R
通讯作者：
Winkler, R
影响因子：
30.8
作者：
Bamforth, SD;Bragança, J;Bhattacharya, S
通讯作者：
Bhattacharya, S
影响因子：
50.5
作者：
Ménard, S;Casalini, P;Tagliabue, E
通讯作者：
Tagliabue, E
DOI：
10.1016/s1357-2725(01)00098-x
发表时间：
2002-01-01
影响因子：
4
作者：
Cheng, C;Ying, K;Mao, YM
通讯作者：
Mao, YM
影响因子：
2.5
作者：
Eceles, SA
通讯作者：
Eceles, SA