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Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2.

ABSTRACT: Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G(1) control and are refractory to Ras(V12)-induced senescence. However, pocket protein-deficient MEFs expressing Ras(V12) 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 G(1) and G(2) 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/p21(CIP1) 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.

SUBMITTER: Vormer TL

PROVIDER: S-EPMC2593436 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2.

Vormer Tinke L TL Foijer Floris F Wielders Camiel L C CL te Riele Hein H

Molecular and cellular biology 20081020 24

Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G(1) control and are refractory to Ras(V12)-induced senescence. However, pocket protein-deficient MEFs expressing Ras(V12) 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 G(1) and G(2) arrest, which could be alleviated by overexpression of ...[more]

PMID: 18936168

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Dataset Information

Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2.

Publications

Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2.

Similar Datasets

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