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Article

Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer

  • Authors:
    • Yuji Ikeda
    • Katsutoshi Oda
    • Osamu Hiraike-Wada
    • Takahiro Koso
    • Aki Miyasaka
    • Tomoko Kashiyama
    • Michihiro Tanikawa
    • Kenbun Sone
    • Kazunori Nagasaka
    • Daichi Maeda
    • Kei Kawana
    • Shunsuke Nakagawa
    • Masashi Fukayama
    • Osamu Tetsu
    • Tomoyuki Fujii
    • Tetsu Yano
    • Shiro Kozuma
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Pathology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Obstetrics and Gynecology, Teikyo University, Tokyo 173-0003, Japan, Cancer Research Institute and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA
  • Pages: 584-588
    |
    Published online on: June 3, 2013
       https://doi.org/10.3892/or.2013.2515
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Abstract

Cyclin D1 is an important regulator of cell cycle progression. Phosphorylation of cyclin D1 at Thr286 by GSK3β triggers its nuclear export and cytoplasmic proteolysis via the 26S proteasome. Cyclin D1 overexpression is a common event in various types of human cancers; however, reports of mutations are extremely rare. We analyzed mutations of the cyclin D1 gene, CCND1, in 88 endometrial cancer tissue specimens and detected mutations in 2 cases (2.3%). Both were unreported mutations with substitution of threonine to isoleucine at codon 286 (T286I). These two tumors harbored coexisting mutations in K-ras, PIK3CA and/or PTEN and showed accumulation of cyclin D1 in the nucleus by immunohistochemistry. Furthermore, we analyzed the functions of mutant cyclin D1 (T286I) by luciferase assays, immunofluorescence, western blotting and clonogenic cell survival assays in HEK-293T cells. We found that exogenous mutant cyclin D1 (T286I) accumulated in the nuclei in HEK-293T cells, and that it inhibited the expression of pRb. Additionally, the number of colonies was increased by introduction of mutant cyclin D1 (T286I) compared to that of wild-type cyclin D1. In conclusion, we identified an unreported CCND1 mutation (T286I) in two endometrial cancers and revealed that the mutation was functional for inducing cell proliferation in human cells.
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1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar

2 

McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF and Rodgers WH: The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol. 106:16–22. 2007. View Article : Google Scholar

3 

Oda K, Stokoe D, Taketani Y and McCormick F: High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 65:10669–10673. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Oda K, Okada J, Timmerman L, et al: PIK3CA cooperates with other phosphatidylinositol 3′-kinase pathway mutations to effect oncogenic transformation. Cancer Res. 68:8127–8136. 2008.

5 

Shoji K, Oda K, Nakagawa S, et al: The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br J Cancer. 101:145–148. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Murayama-Hosokawa S, Oda K, Nakagawa S, et al: Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway. Oncogene. 29:1897–1908. 2010. View Article : Google Scholar

7 

Ikeda Y, Oda K, Nakagawa S, et al: Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer. Int J Gynecol Cancer. 22:725–731. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Malumbres M and Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 9:153–166. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Kato J, Matsushime H, Hiebert SW, Ewen ME and Sherr CJ: Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 7:331–342. 1993. View Article : Google Scholar : PubMed/NCBI

10 

Lundberg AS and Weinberg RA: Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 18:753–761. 1998.

11 

Tetsu O and McCormick F: β-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422–426. 1999.

12 

Albanese C, Johnson J, Watanabe G, et al: Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. J Biol Chem. 270:23589–23597. 1995. View Article : Google Scholar : PubMed/NCBI

13 

Musgrove EA, Caldon CE, Barraclough J, Stone A and Sutherland RL: Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 11:558–572. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Knudsen KE, Diehl JA, Haiman CA and Knudsen ES: Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 25:1620–1628. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Solomon DA, Wang Y, Fox SR, et al: Cyclin D1 splice variants. Differential effects on localization, RB phosphorylation, and cellular transformation. J Biol Chem. 278:30339–30347. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Lu F, Gladden AB and Diehl JA: An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 63:7056–7061. 2003.PubMed/NCBI

17 

Kang S, Kim JW, Park NH, Song YS, Kang SB and Lee HP: Cyclin D1 polymorphism and the risk of endometrial cancer. Gynecol Oncol. 97:431–435. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Benzeno S, Lu F, Guo M, et al: Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1. Oncogene. 25:6291–6303. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Moreno-Bueno G, Rodriguez-Perales S, Sanchez-Estevez C, et al: Cyclin D1 gene (CCND1) mutations in endometrial cancer. Oncogene. 22:6115–6118. 2003. View Article : Google Scholar

20 

Minaguchi T, Yoshikawa H, Oda K, et al: PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas. Clin Cancer Res. 7:2636–2642. 2001.PubMed/NCBI

21 

Tanikawa M, Wada-Hiraike O, Nakagawa S, et al: Multifunctional transcription factor TFII-I is an activator of BRCA1 function. Br J Cancer. 104:1349–1355. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Alt JR, Cleveland JL, Hannink M and Diehl JA: Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev. 14:3102–3114. 2000. View Article : Google Scholar

23 

Gladden AB, Woolery R, Aggarwal P, Wasik MA and Diehl JA: Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma. Oncogene. 25:998–1007. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Hall M and Peters G: Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 68:67–108. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Sherr CJ: Cancer cell cycles. Science. 274:1672–1677. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Bali A, O’Brien PM, Edwards LS, Sutherland RL, Hacker NF and Henshall SM: Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res. 10:5168–5177. 2004.

27 

Ogino S, Nosho K, Irahara N, et al: A cohort study of cyclin D1 expression and prognosis in 602 colon cancer cases. Clin Cancer Res. 15:4431–4438. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Bodrug SE, Warner BJ, Bath ML, Lindeman GJ, Harris AW and Adams JM: Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J. 13:2124–2130. 1994.PubMed/NCBI

29 

Lovec H, Grzeschiczek A, Kowalski MB and Moroy T: Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice. EMBO J. 13:3487–3495. 1994.PubMed/NCBI

30 

Lovec H, Sewing A, Lucibello FC, Muller R and Moroy T: Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene. 9:323–326. 1994.PubMed/NCBI

31 

Uchimaru K, Endo K, Fujinuma H, Zukerberg L, Arnold A and Motokura T: Oncogenic collaboration of the cyclin D1 (PRAD1, bcl-1) gene with a mutated p53 and an activated ras oncogene in neoplastic transformation. Jpn J Cancer Res. 87:459–465. 1996. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ikeda Y, Oda K, Hiraike-Wada O, Koso T, Miyasaka A, Kashiyama T, Tanikawa M, Sone K, Nagasaka K, Maeda D, Maeda D, et al: Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer. Oncol Rep 30: 584-588, 2013.
APA
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T. ... Kozuma, S. (2013). Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer. Oncology Reports, 30, 584-588. https://doi.org/10.3892/or.2013.2515
MLA
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T., Tanikawa, M., Sone, K., Nagasaka, K., Maeda, D., Kawana, K., Nakagawa, S., Fukayama, M., Tetsu, O., Fujii, T., Yano, T., Kozuma, S."Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer". Oncology Reports 30.2 (2013): 584-588.
Chicago
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T., Tanikawa, M., Sone, K., Nagasaka, K., Maeda, D., Kawana, K., Nakagawa, S., Fukayama, M., Tetsu, O., Fujii, T., Yano, T., Kozuma, S."Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer". Oncology Reports 30, no. 2 (2013): 584-588. https://doi.org/10.3892/or.2013.2515
Copy and paste a formatted citation
x
Spandidos Publications style
Ikeda Y, Oda K, Hiraike-Wada O, Koso T, Miyasaka A, Kashiyama T, Tanikawa M, Sone K, Nagasaka K, Maeda D, Maeda D, et al: Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer. Oncol Rep 30: 584-588, 2013.
APA
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T. ... Kozuma, S. (2013). Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer. Oncology Reports, 30, 584-588. https://doi.org/10.3892/or.2013.2515
MLA
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T., Tanikawa, M., Sone, K., Nagasaka, K., Maeda, D., Kawana, K., Nakagawa, S., Fukayama, M., Tetsu, O., Fujii, T., Yano, T., Kozuma, S."Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer". Oncology Reports 30.2 (2013): 584-588.
Chicago
Ikeda, Y., Oda, K., Hiraike-Wada, O., Koso, T., Miyasaka, A., Kashiyama, T., Tanikawa, M., Sone, K., Nagasaka, K., Maeda, D., Kawana, K., Nakagawa, S., Fukayama, M., Tetsu, O., Fujii, T., Yano, T., Kozuma, S."Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer". Oncology Reports 30, no. 2 (2013): 584-588. https://doi.org/10.3892/or.2013.2515
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