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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/4094

Title: The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor-/progesterone receptor-/HER-2- Breast carcinomas
Authors: Verlinden, Lieve
Vanden Bempt, Isabelle
Eelen, Guy
Drijkoningen, Maria
Marchal, Kathleen
De Wolf-Peeters, Christiane
Christiaens, Marie-Rose
Bouillon, Roger
Verstuyf, Annernieke
Issue Date: 2007
Citation: CANCER RESEARCH, 67(14). p. 6574-6581
Abstract: We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D-3, a known inhibitor of cell proliferation. In the present study, we aimed to investigate the transcriptional regulation of Chk1 and Claspin and to study their expression levels in human breast cancer tissue. Transient transfection experiments in MCF-7 breast cancer cells showed that promoter activities of Chk1 and Claspin were regulated by the E2F family of transcription factors. Subsequently, transcript levels of Chk1, Claspin, and E2F1 were determined by quantitative reverse transcriptase-PCR analysis in 103 primary invasive breast carcinomas and were compared with several clinicopathologic variables in breast cancer. A strong correlation was found between Chk1 and Claspin transcript levels. Transcript levels of Chk1, Claspin, and E2F] were highest in histologic grade 3 tumors and in tumors in which the expression of estrogen receptor (ER) and progesterone receptor (PR) was lost. Moreover, Chk1 expression was significantly elevated in grade 3 breast carcinomas showing a triple-negative ER-/PR-/HER-2- phenotype compared with other grade 3 tumors. Further research is warranted to validate the use of Chk1 inhibitors in triple-negative breast carcinomas for which treatment strategies are limited at present.
Notes: Katholieke Univ Leuven, Lab Expt Geneeskunde & Endocrinol, B-3000 Louvain, Belgium. Katholieke Univ Leuven, CMPG ESAT, Louvain, Belgium. Katholieke Univ Leuven, Univ Hosp, Dept Pathol, Louvain, Belgium. Katholieke Univ Leuven, Univ Hosp, Multidisciplinary Breast Ctr, Louvain, Belgium. Katholieke Univ Leuven, Univ Hosp, Dept Surg, Louvain, Belgium. Univ Hasselt, Biomed Res Inst BIOMED, Diepenbeek, Belgium.Verstuyf, A, Katholieke Univ Leuven, Lab Expt Geneeskunde & Endocrinol, Legendo,Bus 902,Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium.Mieke.Verstuyf@med.kuleuven.be
URI: http://hdl.handle.net/1942/4094
DOI: 10.1158/0008-5472.CAN-06-3545
ISI #: 000248319000008
ISSN: 0008-5472
Category: A1
Type: Journal Contribution
Validation: ecoom, 2008
Appears in Collections: Research publications

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