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Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells
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  • Regular Article
  • Open access
  • Published: 12 November 1999

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

  • K K Dhar1,3,
  • K Branigan1,
  • J Parkes2,
  • R E J Howells3,
  • P Hand4,
  • C Musgrove4,
  • R C Strange1,
  • A A Fryer1,
  • C W E Redman3 &
  • …
  • P R Hoban1 

British Journal of Cancer volume 81, pages 1174–1181 (1999)Cite this article

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Summary

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4–19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Barbieri, F, Cagnoli, M, Ragni, N, Pedulla, F, Foglia, G & Alama, A (1997). Expression of cyclin D1 correlates with malignancy in human ovarian tumours. Br J Cancer 75: 1263–1268.

    Article  CAS  Google Scholar 

  • Bellacosa, A, Almadori, G, Cavallo, S, Cadoni, G, Galli, J, Ferrandina, G, Scambia, G & Neri, G (1996). Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications. Clin Cancer Res 2: 175–180.

    CAS  PubMed  Google Scholar 

  • Betticher, DC, Heighway, J, Haselton, PS, Altermatt, HJ, Ryder, WDJ, Cerny, T & Thatcher, N (1996). Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer 73: 294–300.

    Article  CAS  Google Scholar 

  • Betticher, DC, Thatcher, N, Altermatt, HJ, Hoban, P, Ryder, WDJ & Heighway, J (1995). Alternate splicing produces a novel cyclin D1 transcript. Oncogene 11: 1005–1011.

    CAS  PubMed  Google Scholar 

  • Bringuier, PP, Tamimi, YE, Schuuring, E & Schalken, J (1996). Expression of cyclin D1 and EMS1 in bladder tumours: relationship with chromosome 11q13 amplification. Oncogene 12: 1747–1753.

    CAS  PubMed  Google Scholar 

  • Callender, T, El-Naggar, AK, Lee, MS, Frankenthaler, R, Luna, MA & Batsakis, JG (1994). PRAD 1 (CCND1)/Cyclin D1 oncogene amplification in head and neck squamous cell carcinoma. Cancer 74: 152–158.

    Article  CAS  Google Scholar 

  • Chang, J, Bridgewater, J, Gore, M, Fischer, C, Schofield, J, A’Hern, R, Ponder, B, Jacobs, I, McKeage, M, Kelland, L & Harap, K (1994). Non surgical aspects of ovarian cancer. Lancet 343: 335–340.

    Article  Google Scholar 

  • Courjal, F, Louason, G, Speiser, P, Katsaros, D, Zeillinger, R & Theillet, C (1996). Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumours. Int J Cancer 69: 247–253.

    Article  CAS  Google Scholar 

  • de Boer, CJ, Loyson, S, Kluin, PM, Kluin-Nelemans, HC, Schruuring, E & van Krieken, JH (1993). Multiple breakpoints with the bcl-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene. Cancer Res 53: 4148–4152.

    CAS  PubMed  Google Scholar 

  • de Boer, CJ, Schuuring, E, Dreef, E, Peters, G, Bartek, J, Kluin, PM & van Krieken, JH (1995). Cyclin D1 protein analysis in the diagnosis of matel cell lymphoma. Blood 86: 2715–2723.

    CAS  PubMed  Google Scholar 

  • Dhar, KK, Branigan, K, Hand, P, Howells, R, Redman, C, Strange, R, Heighway, J & Hoban, P (1997). Analysis of Cyclin D1 amplification and overexpression in ovarian cancer. Acta Obstet Gynaecol Scand 76: 19

    Google Scholar 

  • Diehl, JA & Sherr, CJ (1997). A dominant-negative mutant prevents nuclear import of cyclin dependent kinase 4 (CDK4) and its phosphorylation by CDK- activating kinase. Mol Cell Biol 17: 7362–7364.

    Article  CAS  Google Scholar 

  • Dulic, V, Drullinger, LF, Lees, E, Reed, SI & Stein, GH (1993). Altered regulation of G1 cyclins in senescent human diploid fibroblasts: accumulation of inactive cyclin E-Cdk2 and cyclin D1-Cdk2 complexes. Proc Natl Acad Sci USA 90: 11034–11038.

    Article  CAS  Google Scholar 

  • Foulkes, WD, Campbell, IG, Stamp, G & Trowsdale, J (1993). Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. Br J Cancer 67: 268–273.

    Article  CAS  Google Scholar 

  • Gabra, H, Watson, JEV, Taylor, KJ, Mackay, J, Leonard, RC, Steel, CM, Porteous, DJ & Smyth, JF (1996). Definition and refinement of loss of heterozygosity at 11q23.3–q24.3 in epithelial ovarian cancer associated with poor prognosis. Cancer Res 56: 950–954.

    CAS  PubMed  Google Scholar 

  • Gansauge, S, Gansauge, F, Ramadani, M, Stobbe, H, Rau, B, Harada, N & Beger, H (1997). Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res 57: 1634–1637.

    CAS  PubMed  Google Scholar 

  • Gillett, C, Fantl, V, Smith, R, Fisher, C, Bartek, J, Dickson, C, Barnes, D & Peters, G (1994). Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 54: 1812–1817.

    CAS  PubMed  Google Scholar 

  • Gillett, C, Smith, P, Gregory, W, Richards, M, Millis, R, Peters, G & Barnes, D (1996). Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69: 92–99.

    Article  CAS  Google Scholar 

  • Howells, REJ, Redman, CWE, Dhar, KK, Sarhanis, P, Musgrove, C, Jones, PW, Alldersea, J, Fryer, AA, Hoban, P & Strange, RC (1998). Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer. Clin Cancer Res 4: 2439–2445.

    CAS  PubMed  Google Scholar 

  • Hung, W-C, Chai, C-Y, Huang, J-S & Chuang, L-Y (1996). Expression of cyclin D1 and c-Ki-ras gene in human epithelial ovarian tumours. Hum Pathol 27: 1324–1328.

    Article  CAS  Google Scholar 

  • Kotelnikov, VM, Coon, JS, Mundle, S, Kelanic, S, LaFollette, S, Taylor, IVS, Hutchinson, J, Panje, W, Caldarelli, DD & Preisler, HD (1997). Cyclin D1 expression in squamous cell carcinomas of the head and neck and in oral mucosa in relation to proliferation and apoptosis. Clin Cancer Res 3: 95–101.

    CAS  PubMed  Google Scholar 

  • Kranenburg, O, van der Eb, AJ & Zantema, A (1996). Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J 15: 46–54.

    Article  CAS  Google Scholar 

  • Kurzrock, R, Ku, S & Talpaz, M (1995). Abnormalities in the PRAD1 (Cyclin D1/ BCL-1) oncogene are frequent in cervical and vulval squamous cell carcinoma cell lines. Cancer 75: 584–590.

    Article  CAS  Google Scholar 

  • Kwon, TK, Buchholz, MA, Gabrielson, EW & Nordin, AA (1995). A novel cytoplasmic substrate for cdk4 and cdk6 in normal and malignant epithelial derived cells. Oncogene 11: 2077–2083.

    CAS  PubMed  Google Scholar 

  • La Baer, J, Garrett, MD, Stevenson, LF, Slingerland, JM, Sandhu, C, Chou, HS, Fattaey, A & Harlow, E (1997). New functional activities for the p21 family of CDK inhibitors. Genes Dev 11: 847–862.

    Article  CAS  Google Scholar 

  • Lukas, J, Bartkova, J, Welcker, M, Peterson, O, Peters, G, Strauss, M & Bartek, J (1995). Cyclin D2 is a moderately oscillating nucleoprotein required for G1 phase progression in specific cell types. Oncogene 10: 2125–2134.

    CAS  PubMed  Google Scholar 

  • Lucibello, FC, Sewing, A, Brusselbach, S, Burger, C & Muller, R (1993). Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts. J Cell Sci 105: 123–133.

    CAS  PubMed  Google Scholar 

  • Masciullo, V, Scambia, G, Marone, M, Giannitelli, C, Ferrandina, G, Bellacosa, A, Bendetti Panici, P & Mancus, OS (1997). Altered expression of cyclin D1 and CDK4 genes in ovarian carcinomas. Int J Cancer 74: 390–395.

    Article  CAS  Google Scholar 

  • Michalides, R, van Veelen, N, Hart, A, Loftus, B, Wientjens, E & Balm, A (1995). Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res 55: 975–978.

    CAS  PubMed  Google Scholar 

  • Motokura, T, Bloom, T, Kim, HG, Juppner, H, Ruderman, JV, Kronenberg, HM & Arnold, A (1991). A novel cyclin encoded by a bcl-1 linked candidate oncogene. Nature 350: 512–515.

    Article  CAS  Google Scholar 

  • Musgrove, EA, Lee, CS, Buckley, MF & Sutherland, RL (1994). Cyclin D1 induction in breast cancer cells shorten G1 and is sufficient for cells arrested in G1 to complete the cell cycle. Proc Natl Acad Sci USA 91: 8022–8026.

    Article  CAS  Google Scholar 

  • Nakamura, S, Seto, M, Banno, S, Suzuki, S, Koshikawa, T, Kitoh, K, Kagami, Y, Ogura, M, Yatabe, Y, Kojima, M, Motoori, T, Takahashi, T, Ueda, R & Suchi, T (1994). Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantel cell lymphoma. Jpn J Cancer Res 85: 1270–1279.

    Article  CAS  Google Scholar 

  • Nishida, N, Fukuda, Y, Komeda, T, Kita, R, Sando, T, Furukawa, M, Amenomori, M, Shibagaki, I, Nakao, K, Ikenaga, M & Ishizaki, K (1994). Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. Cancer Res 54: 3107–3110.

    CAS  PubMed  Google Scholar 

  • Palmero, I & Peters, G (1996). Perturbation of cell cycle regulators in human cancer. Cancer Surveys 27: 351–367.

    CAS  PubMed  Google Scholar 

  • Quelle, DE, Ashmun, RA, Shurtleff, SA, Kato, JY, Bar-Sagi, D, Roussel, MF & Sherr, CJ (1993). Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev 7: 1559–1571.

    Article  CAS  Google Scholar 

  • Sambrook, J, Fritsch, EF & Maniatis, T (1989). Molecular Cloning: A Laboratory Manual, 2nd edn, Cold Spring Harbor Laboratory Press: Cold Spring Harbor NY, USA

    Google Scholar 

  • Sawa, H, Ohshima, TA, Ukita, H, Murakami, H, Chiba, Y, Kamanda, H, Hara, M & Saito, I (1998). Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner. Oncogene 16: 1701–1712.

    Article  CAS  Google Scholar 

  • Sherr, CJ (1996). Cancer cell cycles. Science 274: 1672–1677.

    Article  CAS  Google Scholar 

  • Worsley, S, Ponder, BAJ & Davies, BR (1997). Overexpression of cyclin D1 in epithelial ovarian cancers. Gynecol Oncol 64: 189–195.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Centre for Cell and Molecular Medicine, University of Keele School of Postgraduate Medicine, North Staffordshire Hospital, Stoke-on-Trent, UK

    K K Dhar, K Branigan, R C Strange, A A Fryer & P R Hoban

  2. Department of Pathology, Stafford District General Hospital, Weston Road, Stafford, UK

    J Parkes

  3. Department of Obstetrics and Gynaecology, City General Hospital, Stoke-on-Trent, UK

    K K Dhar, R E J Howells & C W E Redman

  4. Department of Histopathology, Central Pathology Laboratories, Stoke-on-Trent, UK

    P Hand & C Musgrove

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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Dhar, K., Branigan, K., Parkes, J. et al. Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells. Br J Cancer 81, 1174–1181 (1999). https://doi.org/10.1038/sj.bjc.6690826

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  • Received: 12 October 1998

  • Revised: 23 March 1999

  • Accepted: 13 May 1999

  • Published: 12 November 1999

  • Issue date: 01 December 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690826

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Keywords

  • ovarian cancer
  • cyclin D1
  • cytoplasm: nucleus
  • amplification
  • clinical outcome

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