Loss of cyclin E requirement in cell growth of an oral squamous cell carcinoma cell line implies deregulation of its downstream pathway.
Cyclin E and Cdk2 have been shown to play an important role in G1/S transition of the cell cycle. Two E-type cyclins (E1 and E2) have been identified to date and share functionally similarities. Upregulation of these cyclins has been observed frequently in human cancers. We examined the expression profile of cyclin E1 and E2 in cell lines derived from human oral squamous cell carcinoma (SCC), and found that the expression of cyclin E1 protein was hardly detected in HSC-2 cells. Although cyclin E2 was abundantly expressed, histone H1 kinase activities of both E-type cyclins were virtually undetectable in this cell line. Inhibition of cyclin E1, but not that of E2, by using vectors expressing antisense-oriented their cDNAs induced drastic growth suppression on HOC313 cells that express both E-type cyclins. Inhibition of neither cyclin E1 nor E2 suppressed the growth of HSC-2 cells, and compensatory elevation of cyclin E1 was not evident in cyclin E2-inhibited HSC-2 cells. In contrast, HSC-2 cells expressed cyclin D1 and hyperphosphorylated forms of Rb family proteins, and were arrested in G1 by overexpression of p16(INK4), a specific inhibitor against D-type cyclin activity. These results indicate that HSC-2 cells lost proper growth control specifically mediated by cyclin E and suggest that deregulation of its downstream pathway may contribute to tumorigenesis of oral SCC.
Yamada
Shumpei
S
Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Sumrejkanchanakij
Piyamas
P
Amagasa
Teruo
T
Ikeda
Masa-Aki
MA
D002455:Cell Division / Q000235:genetics* / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D019927:Cyclin E; D016213:Cyclins / Q000096:biosynthesis*; D018076:DNA, Complementary; D020869:Gene Expression Profiling; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D018307:Neoplasms, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
C475820:CCNE1 protein, human; C503688:CCNE2 protein, human; D019927:Cyclin E; D016213:Cyclins; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins