title: The impact of cysteine-rich intestinal protein 1 (CRIP1) in human breast cancer.
abstract: BACKGROUND
  CRIP1 (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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Because 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.
authors.affiliation: Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg 85764, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ludyga
authors.forename: Sonja
authors.initials: S
authors.lastname: Englert
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pflieger
authors.forename: Sandra
authors.initials: S
authors.lastname: Rauser
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Michaela
authors.initials: M
authors.lastname: Aubele
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D060588:LIM Domain Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C486181:CRIP1 protein, human