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PMID: 20714219 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Cyclin T1 overexpression induces malignant transformation and tumor growth.

Cell cycle (Georgetown, Tex.) ·Vol. 9 ·No. 15 ·2010-08-01 ·Pages 3119-26

Moiola C, De Luca P, Gardner K, Vazquez E, De Siervi A

Abstract

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.

MeSH Terms
Animals Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic/genetics,pathology Clone Cells Cyclin T/genetics,metabolism Cyclin-Dependent Kinase 4/metabolism Cyclin-Dependent Kinase 9/metabolism Gene Expression Regulation, Neoplastic Head and Neck Neoplasms/enzymology,genetics,pathology Humans Mice NIH 3T3 Cells Neoplasms/metabolism,pathology Phosphorylation Positive Transcriptional Elongation Factor B/metabolism Retinoblastoma Protein/metabolism Tumor Stem Cell Assay Xenograft Model Antitumor Assays
Chemicals
Cyclin T Retinoblastoma Protein Positive Transcriptional Elongation Factor B CDK4 protein, human CDK9 protein, human Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 9
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Moiola Cristian
Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
De Luca Paola
Gardner Kevin
Vazquez Elba
De Siervi Adriana
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Article Info
Journal
Cell cycle (Georgetown, Tex.)
Abbr.
Cell Cycle
ISSN
1551-4005
DOI
10.4161/cc.9.15.12526
Published
2010-08-01
Pages
3119-26
Language
English
Region
United States
NLM ID
101137841
PMCID
PMC3040930
Subset
IM
Corrections
CommentIn
PMID: 20703074
CommentIn
PMID: 20703082
External Links
PubMed source DOI: 10.4161/cc.9.15.12526 PMC Full Text View journal details
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