The impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) in human breast cancer

Molecular Cancer

Research

Gert Auer¹  Herbert Braselmann²  Kerstin Pflieger³  Michaela Aubele³  Sonja Englert³  Natalie Ludyga³  Axel Walch³  Sandra Rauser³  Heinz Höfler⁴ 

[1] Department of Oncology and Pathology, Karolinska Institute and Hospital, S-17176, Stockholm, Sweden;Department of Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany;Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany;Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany;Institute of Pathology, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany;

关键词: CRIP1;    HER2;    ERB-B2;    Breast cancer;    Tumorigenesis;    Prognosis;    Invasion;    RNAi;    RNA interference;    Proliferation;   

DOI  :  10.1186/1476-4598-12-28

 received in 2012-08-20, accepted in 2013-04-01,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCRIP1 (cysteine-rich intestinal protein 1) has been found in several tumor types, its prognostic impact and its role in cellular processes, particularly in breast cancer, are still unclear.MethodsTo elucidate the prognostic impact of CRIP1, we analyzed tissues from 113 primary invasive ductal breast carcinomas using immunohistochemistry. For the functional characterization of CRIP1, its endogenous expression was transiently downregulated in T47D and BT474 breast cancer cells and the effects analyzed by immunoblotting, WST-1 proliferation assay and invasion assay.ResultsWe found a significant correlation between CRIP1 and HER2 (human epidermal growth factor receptor 2) expression levels (p = 0.016) in tumor tissues. In Kaplan Meier analyses, CRIP1 expression was significantly associated with the distant metastases-free survival of patients, revealing a better prognosis for high CRIP1 expression (p = 0.039). Moreover, in multivariate survival analyses, the expression of CRIP1 was an independent negative prognostic factor, along with the positive prognosticators nodal status and tumor size (p = 0.029). CRIP1 knockdown in the T47D and BT474 breast cancer cell lines led to the increased phosphorylation of MAPK and Akt, to the reduced phosphorylation of cdc2, and to a significantly elevated cell proliferation in vitro (p < 0.001). These results indicate that reduced CRIP1 levels may increase cell proliferation and activate cell growth. In addition, CRIP1 knockdown increased cell invasion in vitro.ConclusionsBecause the lack of CRIP1 expression in breast cancer tissue is significantly associated with a worse prognosis for patients and low endogenous CRIP1 levels in vitro increased the malignant potential of breast cancer cells, we hypothesize that CRIP1 may act as a tumor suppressor in proliferation and invasion processes. Therefore, CRIP1 may be an independent prognostic marker with significant predictive power for use in breast cancer therapy.

【 授权许可】

Unknown   
© Ludyga et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.