1. Anchorage-Independent Growth of Pocket Protein-Deficient Murine Fibroblasts Requires Bypass of G2 Arrest and Can Be Accomplished by Expression of TBX2.
- Author
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Vormer, Tinke L., Foijer, Floris, Wielders, Camiel L. C., and Hein te Riele
- Subjects
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FIBROBLASTS , *CONNECTIVE tissue cells , *PROTEIN kinases , *P53 protein , *CELLS , *CYTOLOGY - Abstract
Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G1 control and are refractory to RasV12-induced senescence. However, pocket protein-deficient MEFs expressing RasV12 were unable to exhibit anchorage-independent growth or to form tumors in nude mice. We show that depending on the level of pocket proteins, loss of adhesion induces G1 and G2 arrest, which could be alleviated by overexpression of the TBX2 oncogene. TBX2-induced transformation occurred only in the absence of pocket proteins and could be attributed to downregulation of the p53/p21CIP1 pathway. Our results show that a balance between the pocket protein and p53 pathways determines the level of transformation of MEFs by regulating cyclin-dependent kinase activities. Since transformation of human fibroblasts also requires ablation of both pathways, our results imply that the mechanisms underlying transformation of human and mouse cells are not as different as previously claimed. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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