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| ABNORMAL PATTERNS OF D-TYPE CYCLIN EXPRESSION AND G(1) REGULATION IN HUMAN HEAD AND NECK-CANCER |
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| Author(s): BARTKOVA J, LUKAS J, MULLER H, STRAUSS M, GUSTERSON B, BARTEK J |
| Source: CANCER RESEARCH Volume: 55 Issue: 4 Pages: 949-956 Published: FEB 15 1995 |
| Times Cited: 186 References: 67 |
| Abstract: D-type cyclins are proto-oncogenic cell cycle regulators implicated in the pathogenesis of several types of cancer. Amplification of the cyclin D1 gene has been described in 30-50% of human head and neck squamous cell carcinoma (HNSCC). Using immunohistochemistry on archival specimens of human HNSCC and a mAb DCS-6, which is specific for cyclin D1, strong positivity was found in nuclei of 9 (17%) of 52, a moderately elevated signal in 16 (31%) of 52, and weak staining comparable with normal tissues in 27 (52%) of 52 patients. Immunoblotting analysis of five HNSCC-derived cell lines showed three distinct spectra of D-type cyclin proteins: cyclin D1 only (in UMSCC-2 and UMSCC-22b cell lines with 11q13 amplification), cyclins D1 and D3 (in HN5 and HN6), or cyclins D1, D2, and D3 (in UMSCC-1). Electroporation of neutralizing antibodies demonstrated requirement for cyclin D1 in cell cycle progression of all five HNSCC cell lines. Cyclin D2 was essential and showed a cooperative effect with cyclin D1 in positive regulation of G(1) in UMSCC-1 cells. These data are consistent with the proposed oncogenic role of cyclin D1 in HNSCC and open up the way for immunohistochemical assessment of cyclin D1 aberrations in archival clinical specimens. It is also suggested that excessive levels of cyclin DI alone or cooperative effects of several D-type cyclin proteins may teed to deregulation of G(1) control in distinct subsets of human HNSCC. These results are discussed in the context of possible functional redundancy of D-type cyclins and the role of the D-type cyclin/ p16-CDKN2/pRB pathway in tumorigenesis. |
| Document Type: Article |
| Language: English |
Addresses:
1. DANISH CANC SOC, DIV CANC BIOL, DK-2100 COPENHAGEN O, DENMARK
2. MAX PLANCK GESELL, D-13122 BERLIN, GERMANY
3. INST CANC RES, HADDOW LABS, SUTTON SM2 5NG, SURREY ENGLAND |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: QG003 |
| ISSN: 0008-5472 |
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