Abstract
Aims—To determine cyclin D1 gene amplification and expression levels in head and neck squamous cell carcinoma (HNSCC) patients.
Methods—Total RNA and genomic DNA were isolated from 40 samples of HNSCC tissue and matched normal tissue and were hybridised with a cyclin D1 cDNA probe. Northern and Southern analyses were used to detect mRNA overexpression and cyclin D1 gene amplification, respectively.
Results—15 of the 40 HNSCC samples examined (38%) showed cyclin D1 gene amplification. Of these 15 samples, all 13 from which RNA was available showed increased cyclin D1 expression.
Conclusions—HNSCC patients with both amplification and overexpression of the cyclin D1 gene are at greater risk than patients who showed no cyclin D1 gene amplification; amplification and over-expression of the cyclin D1 gene may play an important role in the progression of HNSCC and in clinical outcome.
Keywords: cyclin D1
Keywords: head and neck squamous cell carcinoma
Keywords: gene amplification
Keywords: mRNA overexpression
Keywords: tumour progression
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- Baldin V., Lukas J., Marcote M. J., Pagano M., Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993 May;7(5):812–821. doi: 10.1101/gad.7.5.812. [DOI] [PubMed] [Google Scholar]
- Berenson J. R., Koga H., Yang J., Pearl J., Holmes E. C., Figlin R. Frequent amplification of the bcl-1 locus in poorly differentiated squamous cell carcinoma of the lung. The Lung Cancer Study Group. Oncogene. 1990 Sep;5(9):1343–1348. [PubMed] [Google Scholar]
- Berenson J. R., Yang J., Mickel R. A. Frequent amplification of the bcl-1 locus in head and neck squamous cell carcinomas. Oncogene. 1989 Sep;4(9):1111–1116. [PubMed] [Google Scholar]
- Buckley M. F., Sweeney K. J., Hamilton J. A., Sini R. L., Manning D. L., Nicholson R. I., deFazio A., Watts C. K., Musgrove E. A., Sutherland R. L. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993 Aug;8(8):2127–2133. [PubMed] [Google Scholar]
- Faust J. B., Meeker T. C. Amplification and expression of the bcl-1 gene in human solid tumor cell lines. Cancer Res. 1992 May 1;52(9):2460–2463. [PubMed] [Google Scholar]
- Gillett C., Fantl V., Smith R., Fisher C., Bartek J., Dickson C., Barnes D., Peters G. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 1994 Apr 1;54(7):1812–1817. [PubMed] [Google Scholar]
- Hinds P. W., Dowdy S. F., Eaton E. N., Arnold A., Weinberg R. A. Function of a human cyclin gene as an oncogene. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):709–713. doi: 10.1073/pnas.91.2.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jares P., Fernández P. L., Campo E., Nadal A., Bosch F., Aiza G., Nayach I., Traserra J., Cardesa A. PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas. Cancer Res. 1994 Sep 1;54(17):4813–4817. [PubMed] [Google Scholar]
- Jiang W., Kahn S. M., Tomita N., Zhang Y. J., Lu S. H., Weinstein I. B. Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res. 1992 May 15;52(10):2980–2983. [PubMed] [Google Scholar]
- Jiang W., Kahn S. M., Zhou P., Zhang Y. J., Cacace A. M., Infante A. S., Doi S., Santella R. M., Weinstein I. B. Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression. Oncogene. 1993 Dec;8(12):3447–3457. [PubMed] [Google Scholar]
- Jiang W., Zhang Y. J., Kahn S. M., Hollstein M. C., Santella R. M., Lu S. H., Harris C. C., Montesano R., Weinstein I. B. Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9026–9030. doi: 10.1073/pnas.90.19.9026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leonard J. H., Kearsley J. H., Chenevix-Trench G., Hayward N. K. Analysis of gene amplification in head-and-neck squamous-cell carcinoma. Int J Cancer. 1991 Jun 19;48(4):511–515. doi: 10.1002/ijc.2910480406. [DOI] [PubMed] [Google Scholar]
- Lovec H., Sewing A., Lucibello F. C., Müller R., Möröy T. Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene. 1994 Jan;9(1):323–326. [PubMed] [Google Scholar]
- Michalides R., van Veelen N., Hart A., Loftus B., Wientjens E., Balm A. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res. 1995 Mar 1;55(5):975–978. [PubMed] [Google Scholar]
- Motokura T., Arnold A. Cyclin D and oncogenesis. Curr Opin Genet Dev. 1993 Feb;3(1):5–10. doi: 10.1016/s0959-437x(05)80334-x. [DOI] [PubMed] [Google Scholar]
- Motokura T., Bloom T., Kim H. G., Jüppner H., Ruderman J. V., Kronenberg H. M., Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512–515. doi: 10.1038/350512a0. [DOI] [PubMed] [Google Scholar]
- Nishida N., Fukuda Y., Komeda T., Kita R., Sando T., Furukawa M., Amenomori M., Shibagaki I., Nakao K., Ikenaga M. Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. Cancer Res. 1994 Jun 15;54(12):3107–3110. [PubMed] [Google Scholar]
- Proctor A. J., Coombs L. M., Cairns J. P., Knowles M. A. Amplification at chromosome 11q13 in transitional cell tumours of the bladder. Oncogene. 1991 May;6(5):789–795. [PubMed] [Google Scholar]
- Quelle D. E., Ashmun R. A., Shurtleff S. A., Kato J. Y., Bar-Sagi D., Roussel M. F., Sherr C. J. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev. 1993 Aug;7(8):1559–1571. doi: 10.1101/gad.7.8.1559. [DOI] [PubMed] [Google Scholar]
- Resnitzky D., Gossen M., Bujard H., Reed S. I. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol Cell Biol. 1994 Mar;14(3):1669–1679. doi: 10.1128/mcb.14.3.1669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rothman K. J. The effect of alcohol consumption on risk of cancer of the head and neck. Laryngoscope. 1978 Jan;88(1 Pt 2 Suppl 8):51–55. [PubMed] [Google Scholar]
- Schuuring E., Verhoeven E., Mooi W. J., Michalides R. J. Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene. 1992 Feb;7(2):355–361. [PubMed] [Google Scholar]
- Schuuring E., Verhoeven E., van Tinteren H., Peterse J. L., Nunnink B., Thunnissen F. B., Devilee P., Cornelisse C. J., van de Vijver M. J., Mooi W. J. Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. Cancer Res. 1992 Oct 1;52(19):5229–5234. [PubMed] [Google Scholar]
- Sherr C. J. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. doi: 10.1016/0092-8674(93)90636-5. [DOI] [PubMed] [Google Scholar]
- Somers K. D., Cartwright S. L., Schechter G. L. Amplification of the int-2 gene in human head and neck squamous cell carcinomas. Oncogene. 1990 Jun;5(6):915–920. [PubMed] [Google Scholar]
- Wang T. C., Cardiff R. D., Zukerberg L., Lees E., Arnold A., Schmidt E. V. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994 Jun 23;369(6482):669–671. doi: 10.1038/369669a0. [DOI] [PubMed] [Google Scholar]
- Williams M. E., Gaffey M. J., Weiss L. M., Wilczynski S. P., Schuuring E., Levine P. A. Chromosome 11Q13 amplification in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1993 Nov;119(11):1238–1243. doi: 10.1001/archotol.1993.01880230084013. [DOI] [PubMed] [Google Scholar]
- Williams M. E., Swerdlow S. H., Rosenberg C. L., Arnold A. Chromosome 11 translocation breakpoints at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma. Leukemia. 1993 Feb;7(2):241–245. [PubMed] [Google Scholar]
- Zhang Y. J., Jiang W., Chen C. J., Lee C. S., Kahn S. M., Santella R. M., Weinstein I. B. Amplification and overexpression of cyclin D1 in human hepatocellular carcinoma. Biochem Biophys Res Commun. 1993 Oct 29;196(2):1010–1016. doi: 10.1006/bbrc.1993.2350. [DOI] [PubMed] [Google Scholar]
- Zhou D. J., Casey G., Cline M. J. Amplification of human int-2 in breast cancers and squamous carcinomas. Oncogene. 1988 Mar;2(3):279–282. [PubMed] [Google Scholar]