Abnormal Patterns of D-Type Cyclin Expression and G1 Regulation in Human Head and Neck Cancer

作者: Jirina Bartkova , Jiri Lukas , Jiri Bartek , Barry Gusterson , Heiko Müller

DOI:

关键词: BiologyCyclin ECyclinCyclin A2Cyclin ACyclin BCancer researchCyclin D1PathologyCyclin DCyclin D2

摘要: Abstract D-type cyclins are proto-oncogenic cell cycle regulators implicated in the pathogenesis of several types cancer. Amplification cyclin D1 gene has been described 30–50% human head and neck squamous carcinoma (HNSCC). Using immunohistochemistry on archival specimens HNSCC a mAb DCS-6, which is specific for D1, strong positivity was found nuclei 9 (17%) 52, moderately elevated signal 16 (31%) weak staining comparable with normal tissues 27 (52%) 52 patients. Immunoblotting analysis five HNSCC-derived lines showed three distinct spectra proteins: only (in UMSCC-2 UMSCC-22b 11q13 amplification), D3 HN5 HN6), or D2, UMSCC-1). Electroporation neutralizing antibodies demonstrated requirement progression all lines. Cyclin D2 essential cooperative effect positive regulation G 1 UMSCC-1 cells. These data consistent proposed oncogenic role open up way immunohistochemical assessment aberrations clinical specimens. It also suggested that excessive levels alone effects proteins may lead to deregulation control subsets HNSCC. results discussed context possible functional redundancy cyclin/p16-CDKN2/pRB pathway tumorigenesis.

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