Epidermal growth factor receptor (EGFR) signalling is a highly regulated process with a tight balance between receptor activation and inactivation in invasive breast carcinomas (IBCs) particularly in triple-negative carcinomas (TNC). Clinical trials using anti-EGFR therapies are actually performed although no activating alterations (mutations, amplifications, or rearrangements) of EGFR have been clearly recognized in order to identify new targeted modalities for IBCs. We explored mammary-derived growth inhibitor (MDGI), estrogen-induced gene-121 (EIG121), and mitogen-induced gene-6 (MIG6), three posttranslational EGFR trafficking molecules implicated in EGFR spatiotemporal regulatory pathway. We quantified MDGI, EIG121, and MIG6 at mRNA levels by using real-time quantitative RT-PCR in a series of 440 IBCs and at protein levels by using immunohistochemistry in a series of 88 IBCs. Results obtained by RT-PCR showed that in IBCs, MDGI, MIG6, and EIG121 mRNA were mainly underexpressed (25.7%, 45.0%, and 16.1%, respectively) particularly in the TNC subtype for EIG121 (60.3%). We also observed mRNA overexpression of MDGI and EIG121, respectively, in 12.7% and 22.3% of IBCs. These altered mRNA expressions were confirmed at the protein level. Some links were found between expression patterns of these three genes and several classical pathological and clinical parameters. Only EIG121 was found to have a prognostic significance (). Altered expression of these three major EGFR posttranslational negative regulators could create an aberrant EGFR-mediated oncogenic signalling pathway in IBCs. MDGI, MIG6, and EIG121 expression status also may be potential useful biomarkers (sensitivity or resistance) in targeted EGFR therapy.

中文翻译：

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侵袭性乳腺癌中三种EGFR翻译后调节因子MDGI，MIG6和EIG121的表达改变。

表皮生长因子受体（EGFR）信号传导是一个高度调控的过程，在浸润性乳腺癌（IBC）中，特别是在三阴性癌（TNC）中，受体激活与失活之间有着紧密的平衡。尽管尚未明确认识到EGFR的激活性改变（突变，扩增或重排）以识别IBC的新靶向方式，但实际上已进行了使用抗EGFR疗法的临床试验。我们探讨了乳腺衍生生长抑制剂（MDGI），雌激素诱导基因121（EIG121）和促分裂原诱导基因6（MIG6），这三个翻译后EGFR转运分子与EGFR时空调节途径有关。我们量化了MDGI，EIG121和MIG6在一系列440个IBC中使用实时定量RT-PCR检测mRNA水平，在一系列88个IBC中使用免疫组织化学检测蛋白水平。通过RT-PCR获得的结果表明，在IBC中，MDGI，MIG6和EIG121 mRNA主要表达不足（分别为25.7％，45.0％和16.1％），特别是在EIG121的TNC亚型中（60.3％）。我们还观察到分别在12.7％和22.3％的IBC中，MDGI和EIG121的mRNA过表达。这些改变的mRNA表达在蛋白质水平被证实。在这三个基因的表达模式与一些经典的病理和临床参数之间发现了一些联系。只有EIG121 被发现具有预后意义（）。这三种主要的EGFR翻译后负调控因子的表达改变可能会在IBCs中产生异常的EGFR介导的致癌信号通路。MDGI，MIG6和EIG121表达状态也可能是靶向EGFR治疗中潜在的有用生物标志物（敏感性或耐药性）。