Sixou Sophie, Müller Katharina, Jalaguier Stéphan, Kuhn Christina, Harbeck Nadia, Mayr Doris, Engel Jutta, Jeschke Udo, Ditsch Nina, Cavaillès Vincent
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Maistrasse 11, D-80337 München, Germany; Université Paul Sabatier Toulouse III, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse cedex 09, France.
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Maistrasse 11, D-80337 München, Germany.
Transl Oncol. 2018 Oct;11(5):1090-1096. doi: 10.1016/j.tranon.2018.06.006. Epub 2018 Jul 11.
New markers are needed to improve diagnosis and to personalize treatments for patients with breast cancer (BC). Receptor-interacting protein of 140 kDa (RIP140) and ligand-dependent corepressor (LCoR), two transcriptional co-regulators of estrogen receptors, strongly interact in BC cells. Although their role in cancer progression has been outlined in the last few years, their function in BC has not been elucidated yet. In this study, we investigated RIP140 and LCoR localization (cytoplasm vs nucleus) in BC samples from a well-characterized cohort of patients (n = 320). RIP140 and LCoR were expressed in more than 80% of tumors, (predominantly in the cytoplasm), and the two markers were highly correlated. Expression of RIP140 and LCoR in the nucleus was negatively correlated with tumor size. Conversely, RIP140 and LCoR cytoplasmic expression strongly correlated with expression of two tumor aggressiveness markers: N-cadherin and CD133 (epithelial mesenchymal transition and cancer stem cell markers, respectively). Finally, high RIP140 nuclear expression was significantly correlated with longer overall survival, whereas high total or cytoplasmic expression of RIP140 was associated with shorter disease-free survival. Our study strongly suggests that the role of RIP140 and LCoR in BC progression could vary according to their prevalent sub-cellular localization, with opposite prognostic values for nuclear and cytoplasmic expression. The involvement in BC progression/invasiveness of cytoplasmic RIP140 could be balanced by the anti-tumor action of nuclear RIP140, thus explaining the previous contradictory findings about its role in BC.
需要新的标志物来改善乳腺癌（BC）患者的诊断并实现个性化治疗。140 kDa的受体相互作用蛋白（RIP140）和配体依赖性共抑制因子（LCoR）是雌激素受体的两种转录共调节因子，它们在BC细胞中强烈相互作用。尽管在过去几年中已经概述了它们在癌症进展中的作用，但它们在BC中的功能尚未阐明。在本研究中，我们调查了来自一个特征明确的患者队列（n = 320）的BC样本中RIP140和LCoR的定位（细胞质与细胞核）。RIP140和LCoR在超过80%的肿瘤中表达（主要在细胞质中），并且这两种标志物高度相关。RIP140和LCoR在细胞核中的表达与肿瘤大小呈负相关。相反，RIP140和LCoR的细胞质表达与两种肿瘤侵袭性标志物的表达密切相关：N-钙黏蛋白和CD133（分别为上皮-间质转化和癌症干细胞标志物）。最后，RIP140的高核表达与更长的总生存期显著相关，而RIP140的高总表达或细胞质表达与更短的无病生存期相关。我们的研究强烈表明，RIP140和LCoR在BC进展中的作用可能因其主要的亚细胞定位而异，细胞核和细胞质表达具有相反的预后价值。细胞质RIP140对BC进展/侵袭性涉及可能被细胞核RIP140的抗肿瘤作用所平衡，从而解释了先前关于其在BC中作用的矛盾发现。
