Cyclin T1 overexpression induces malignant  transformation and tumor growth.
Human PTE Fb is a protein kinase composed by CDK9 and Cyclin T that controls the elongation phase of RNA Pol II. This complex also affects the activation and differentiation program of lymphoid cells. In this study we found that several head and neck tumor cell lines overexpress PTE Fb. We also established that Cyclin T1 is able to induce transformation in vitro, as we determined by foci and colony formation assays. Nu/nu mice s.c. injected with stable transfected Cyclin T1 cells (NIH 3T3 Cyclin T1) developed tumors faster than animals injected with control cells (NIH 3T3 beta-gal). In vitro, NIH 3T3 Cyclin T1 cells show increased proliferation and CDK4-Rb phosphorylation. Even more, silencing E2F1 expression (shRNA E2F1) in NIH 3T3 cells resulted in a dramatic inhibition of Cyclin T1-induced foci. All these data demonstrate for the first time the Cyclin T1 oncogenic function and suggest a role for this protein in controlling cell cycle probably via Rb/E2F1 pathway.
Moiola
Cristian
C
Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
De Luca
Paola
P
Gardner
Kevin
K
Vazquez
Elba
E
De Siervi
Adriana
A
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002999:Clone Cells; D056906:Cyclin T / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D056906:Cyclin T; D016160:Retinoblastoma Protein; D042925:Positive Transcriptional Elongation Factor B; C495900:CDK4 protein, human; C467969:CDK9 protein, human; D051358:Cyclin-Dependent Kinase 4; D042863:Cyclin-Dependent Kinase 9