Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor
Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor
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DOI：
10.1677/erc-06-0005
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发表时间：
2007-06-01
影响因子：
3.9
通讯作者：
Sasano, Hironobu
中科院分区：
文献类型：
--
作者：
Suzuki, Takashi;Inoue, Akio;Sasano, Hironobu
早期生长反应基因3（EGR 3）是一种锌指转录因子，在细胞生长和分化中起重要作用。我们最近证明了雌激素介导的乳腺癌细胞中的EGR 3诱导。然而，EGR 3尚未在乳腺癌组织中检测，其意义仍然未知。因此，在本研究中，我们通过免疫组织化学、体外研究和裸鼠移植瘤模型来研究EGFR 3在乳腺癌中的生物学功能。在190例乳腺癌组织中，99例（52%）的癌细胞中检测到EGR 3免疫反应性，并与mRNA水平相关。EGFR 3免疫反应性与淋巴结状态、远处转移到其他器官、雌激素受体a或同一患者中异步复发病灶中的EGFR 3免疫反应性呈正相关，与小管形成呈负相关。通过单因素和多因素分析，EGFR 3免疫反应性与复发风险增加和不良临床结局显著相关。来自MCF-7 Tet-Off细胞的表达Egr 3的细胞系（Eg-10和Eg-11）根据强力霉素的处理显著增强了迁移和侵袭特性，但没有显著改变细胞增殖。此外，注射到无胸腺小鼠的Eg-11细胞不规则地侵入到邻近的腹膜组织中，尽管用空载体稳定转染的Clt-7作为对照，显示出良好限制的肿瘤。Eg-11细胞与异种移植模型中的侵袭性成分和较少的小管形成显著相关。这些结果表明，EGFR 3在雌激素介导的侵袭中起重要作用，并且是乳腺癌的独立预后因子。
Early growth responsive gene 3 (EGR3) is a zinc-finger transcription factor and plays important roles in cellular growth and differentiation. We recently demonstrated estrogen-mediated induction of EGR3 in breast carcinoma cells. However, EGR3 has not yet been examined in breast carcinoma tissues and its significance remains unknown. Therefore, in this study, we examined biological functions of EGR3 in the breast carcinoma by immunohistochemistry, in vitro study, and nude mouse xenograft model. EGR3 immunoreactivity was detected in carcinoma cells in 99 (52%) out of 190 breast carcinoma tissues and was associated with the mRNA level. EGR3 immunoreactivity was positively associated with lymph node status, distant metastasis into other organs, estrogen receptor a, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negatively correlated with tubule formation. EGR3 immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- and multivariate analyses. Egr3-expressing transformant cell lines derived from MCF-7 Tet-Off cells (Eg-10 and Eg-11) significantly enhanced the migration and invasion properties according to the treatment of doxycyclin, but did not significantly change the cell proliferation. Moreover, Eg-11 cells injected into athymic mice irregularly invaded into the adjacent periturnoral tissues, although Clt-7, which was stably transfected with empty vector as a control, demonstrated a well-circumscribed tumor. Eg-11 cells were significantly associated with invasive components and less tubule formation in the xenograft model. These results suggest that EGR3 plays an important role in estrogen-meditated invasion and is an independent prognostic factor in breast carcinoma.