This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Coco Martin, J. M. Articles by Michalides, R. Search for Related Content PubMed PubMed Citation Articles by Coco Martin, J. M. Articles by Michalides, R.

Cyclin D1 Overexpression Enhances Radiation-induced Apoptosis and Radiosensitivity in a Breast Tumor Cell Line¹

Divisions of Experimental Therapy [J. M. C. M.] and Tumor Biology [A. B., T. V., F. L., R. M.], The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands

Overexpression of cyclin D1, a G₁ cell cycle regulator, is often found in many different tumor types, such as breast carcinoma and squamous cell carcinoma of the head and neck. The overexpression of this protein is, in several cases, associated with a poor prognosis. In this study, the effect of cyclin D1 on radiosensitivity was investigated in a breast tumor cell line, MCF7, containing a cyclin D1 gene construct under the control of a tetracycline-sensitive regulator. MCF7 cells cultured without tetracycline resulted in a 6-fold increase in the cyclin D1 protein.

Cyclin D1-overexpressing MCF7 cells were more sensitive to ionizing radiation than the nonoverexpressing counterparts. The cyclin D1-overexpressing cells also exhibited a higher induction of apoptosis. Treatment with a dose of 5 Gy resulted in a rapid increase of p53 and p21 in the cyclin D1-overexpressing cells. Nonoverexpressing cells showed a more transient expression of these proteins after ionizing radiation. A pronounced G₂-M block was observed in both cell lines. The cyclin D1-overexpressing cells were, however, released earlier from the block than the control cells.

These data suggest that overexpression of cyclin D1 alters sensitivity toward ionizing radiation by modulating -radiation-induced G₂-M transition.

This article has been cited by other articles:

				A. Thakur, Y. Sun, A. Bollig, J. Wu, H. Biliran, S. Banerjee, F. H. Sarkar, and D. J. Liao Anti-invasive and Antimetastatic Activities of Ribosomal Protein S6 Kinase 4 in Breast Cancer Cells Clin. Cancer Res., July 15, 2008; 14(14): 4427 - 4436. [Abstract] [Full Text] [PDF]

				S. Trent, C. Yang, C. Li, M. Lynch, and E. V. Schmidt Heat Shock Protein B8, a Cyclin-Dependent Kinase Independent Cyclin D1 Target Gene, Contributes to Its Effects on Radiation Sensitivity Cancer Res., November 15, 2007; 67(22): 10774 - 10781. [Abstract] [Full Text] [PDF]

				N. M. Probst-Hensch, C.-L. Sun, D. V. D. Berg, M. Ceschi, W.-P. Koh, and M. C. Yu The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study Carcinogenesis, December 1, 2006; 27(12): 2475 - 2482. [Abstract] [Full Text] [PDF]

				R. J. Hung, P. Boffetta, F. Canzian, N. Moullan, N. Szeszenia-Dabrowska, D. Zaridze, J. Lissowska, P. Rudnai, E. Fabianova, D. Mates, et al. Sequence Variants in Cell Cycle Control Pathway, X-ray Exposure, and Lung Cancer Risk: A Multicenter Case-Control Study in Central Europe Cancer Res., August 15, 2006; 66(16): 8280 - 8286. [Abstract] [Full Text] [PDF]

				M. Ceschi, C.-L. Sun, D. Van Den Berg, W.-P. Koh, M. C. Yu, and N. Probst-Hensch The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore Carcinogenesis, August 1, 2005; 26(8): 1457 - 1464. [Abstract] [Full Text] [PDF]

				A. Arnold and A. Papanikolaou Cyclin D1 in Breast Cancer Pathogenesis J. Clin. Oncol., June 20, 2005; 23(18): 4215 - 4224. [Abstract] [Full Text] [PDF]

				T. Choudhuri, S. Pal, T. Das, and G. Sa Curcumin Selectively Induces Apoptosis in Deregulated Cyclin D1-expressed Cells at G2 Phase of Cell Cycle in a p53-dependent Manner J. Biol. Chem., May 20, 2005; 280(20): 20059 - 20068. [Abstract] [Full Text] [PDF]

				S. Sadetzki, P. Flint-Richter, S. Starinsky, I. Novikov, Y. Lerman, B. Goldman, and E. Friedman Genotyping of Patients with Sporadic and Radiation-Associated Meningiomas Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 969 - 976. [Abstract] [Full Text] [PDF]

				C.-F. Hwang, C.-L. Cho, C.-C. Huang, J.-S. Wang, Y.-L. Shih, C.-Y. Su, and H.-W. Chang Loss of cyclin D1 and p16 expression correlates with local recurrence in nasopharyngeal carcinoma following radiotherapy Ann. Onc., August 1, 2002; 13(8): 1246 - 1251. [Abstract] [Full Text] [PDF]

				Y. Zheng, H. Shen, E. M. Sturgis, L.-E Wang, S. A. Eicher, S. S. Strom, M. L. Frazier, M. R. Spitz, and Q. Wei Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case-control study Carcinogenesis, August 1, 2001; 22(8): 1195 - 1199. [Abstract] [Full Text] [PDF]

				H. Miyata, Y. Doki, H. Shiozaki, M. Inoue, M. Yano, Y. Fujiwara, H. Yamamoto, K. Nishioka, K. Kishi, and M. Monden CDC25B and p53 Are Independently Implicated in Radiation Sensitivity for Human Esophageal Cancers Clin. Cancer Res., December 1, 2000; 6(12): 4859 - 4865. [Abstract] [Full Text]

				Q. Zhou, P. Fukushima, W. DeGraff, J. B. Mitchell, M. Stetler-Stevenson, A. Ashkenazi, and P. S. Steeg Radiation and the Apo2L/TRAIL Apoptotic Pathway Preferentially Inhibit the Colonization of Premalignant Human Breast Cells Overexpressing Cyclin D1 Cancer Res., May 1, 2000; 60(10): 2611 - 2615. [Abstract] [Full Text]