Cre/<i>loxP</i>‐mediated inactivation of the murine <i>Pten</i> tumor suppressor gene

Lesche, Ralf; Groszer, Matthias; Gao, Jing; Wang, Ying; Messing, Albee; Sun, Hong; Liu, Xin; Wu, Hong

doi:10.1002/gene.10036

Cited by 362 publications

(363 citation statements)

References 6 publications

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“…VEC-Cre + transgenic mice (129/C57 mixed background) 7 were carefully analysed and confirmed without any aberrant phenotypes before being crossed to Pten loxP/loxP mice (129/ Balb/c mixed background) 24 to obtain Pten loxP/+ ;VEC-Cre + mice, which were backcrossed to Pten loxP/loxP mice to obtain Pten loxP/loxP ;VEC-Cre + mutant mice for this study. We also crossed Pten loxP/loxP ;VEC-Cre + mice with ROSA26-LacZ + reporter transgenic mice 9 , to obtain mice of Pten loxP/loxP ;VEC-Cre + ;LacZ + , Pten +/+ ;VEC-Cre + ;LacZ + and Pten loxP/loxP ;VECCre − ;LacZ + for transplantation and FACS-Gal analysis.…”

Section: Micementioning

confidence: 99%

Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation

Guo¹,

Lasky²,

Chang³

et al. 2008

Nature

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Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance 1 . The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self-renewable leukaemia stem cells (LSCs) are enriched in the c-Kit mid CD3 + Lin − compartment, where unphosphorylated β-catenin is significantly increased. Conditional ablation of one allele of the β-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the β-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit mid CD3 + Lin − LSCs and CD3 + leukaemic blasts,

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Section: Micementioning

confidence: 99%

Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation

Guo¹,

Lasky²,

Chang³

et al. 2008

Nature

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222

261

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“…To examine the influence of PTEN on cyclin D expression, two sets of wild-type and Pten-null mouse embryonic fibroblasts (MEF) were used: Pten þ / þ and Pten À/À that were derived from the mice with conventional gene disruption; wild-type Pten-containing loxp and Pten-null Dloxp that were from the mice with conditional knockout (Sun et al, 1999;Lesche et al, 2002). Reverse transcription-polymerase chain reaction (RT-PCR) was employed to analyse the levels of cylin D1, cyclin D2 and p21 CIP1 in these MEFs.…”

Section: Pten Suppresses Cyclin D2 Expressionmentioning

confidence: 99%

GSK3β mediates suppression of cyclin D2 expression by tumor suppressor PTEN

Huang

et al. 2006

Oncogene

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PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in various types of cancers. It is reported to regulate G1 to S phase transition of the cell cycle by influencing the expression, protein stability and subcellular location of cyclin D1. Here, we provide evidence that PTEN modulates the transcription and protein stability of cyclin D2. Targeted deletion of Pten in mouse embryonic fibroblasts (MEFs) endowed cells with greater potential to overcome G1 arrest than wild-type MEFs and led to the elevated expression of cyclin D2, which was suppressed by the introduction of PTEN. We further defined a pathway involving GSK3b and b-catenin/TCF in PTEN-mediated suppression of cyclin D2 transcription. LiCl, an inhibitor of GSK3b, abolished inhibitory effect of PTEN on cyclin D2 expression, and TCF members could directly bind to the promoter of cyclin D2 and regulate its transcription in a CREB-dependent manner. Our results indicate that the downregulation of cyclin D2 expression by PTEN is mediated by the GSK3b/b-catenin/TCF pathway in cooperation with CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt pathway in modulation of cyclin D2 expression.

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“…The functional domain of a tumor suppressor gene was deleted in the brain using a Cre/ loxP system. 7,8 This approach allowed the authors to study the deletion of this gene in the brain while the conventional deletion of this gene produced a lethal phenotype. 9 Many others have demonstrated that conditional gene activation or deletion can be achieved by crossing transgenic mice that have the gene of interest flanked by two loxP elements with Cre recombinase-expressing transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

“…9 Many others have demonstrated that conditional gene activation or deletion can be achieved by crossing transgenic mice that have the gene of interest flanked by two loxP elements with Cre recombinase-expressing transgenic mice. 8,10 In addition, conditional gene activation or deletions have also been achieved by adenoviral delivery of Cre recombinase in transgenic mice carrying the floxed gene. 11 Delivery of genes by means of adenovirus-based vectors was shown to be highly efficient and applicable to a wide variety of cells types, in cell culture and in vivo in living animals.…”

Section: Introductionmentioning

confidence: 99%