This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verlinden, L. Articles by Verstuyf, A. Search for Related Content PubMed PubMed Citation Articles by Verlinden, L. Articles by Verstuyf, A.

The E2F-Regulated Gene Chk1 Is Highly Expressed in Triple-Negative Estrogen Receptor–/Progesterone Receptor–/HER-2– Breast Carcinomas

¹ Laboratorium voor Experimentele Geneeskunde en Endocrinologie and ² CMPG/ESAT, Katholieke Universiteit Leuven; ³ Department of Pathology, ⁴ Multidisciplinary Breast Centre, and ⁵ Department of Surgery, University Hospital of the Katholieke Universiteit Leuven, Leuven, Belgium; and ⁶ Biomedical Research Institute BIOMED, Universiteit Hasselt, Diepenbeek, Belgium

Requests for reprints: Annemieke Verstuyf, Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Legendo, bus 902, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Phone: 32-16-346163; E-mail: Mieke.Verstuyf{at}med.kuleuven.be.

We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D₃, 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 E2F1 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. [Cancer Res 2007;67(14):6574–81]

This article has been cited by other articles:

				H. Gali-Muhtasib, D. Kuester, C. Mawrin, K. Bajbouj, A. Diestel, M. Ocker, C. Habold, C. Foltzer-Jourdainne, P. Schoenfeld, B. Peters, et al. Thymoquinone Triggers Inactivation of the Stress Response Pathway Sensor CHEK1 and Contributes to Apoptosis in Colorectal Cancer Cells Cancer Res., July 15, 2008; 68(14): 5609 - 5618. [Abstract] [Full Text] [PDF]

				S. Ashwell and S. Zabludoff DNA Damage Detection and Repair Pathways--Recent Advances with Inhibitors of Checkpoint Kinases in Cancer Therapy Clin. Cancer Res., July 1, 2008; 14(13): 4032 - 4037. [Abstract] [Full Text] [PDF]

				D. Ray and H. Kiyokawa CDC25A Phosphatase: a Rate-Limiting Oncogene That Determines Genomic Stability Cancer Res., March 1, 2008; 68(5): 1251 - 1253. [Abstract] [Full Text] [PDF]