Transforming pathways activated by the v-Abl tyrosine kinase

Shore, Scott K.; Tantravahi, Ramana; Reddy, E. Premkumar

doi:10.1038/sj.onc.1206084

Cited by 37 publications

(32 citation statements)

References 92 publications

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“…Acute transforming retroviruses induce polyclonal tumours within 2 to 3 weeks after infection of the host. Transformation by these viruses is mediated by the expression of viral oncogenes such as v-Abl in the Abelson Murine leukaemia Virus (reviewed in Shore et al, 2002), and v-Myb from the avian myoblastosis virus (reviewed in Lipsick and Wang, 1999), which are virally encoded oncogenic versions of normal cellular genes. In contrast, slow transforming retroviruses induce mono-or oligoclonal tumours with a longer latency of 3-12 months.…”

Section: Transforming Retroviruses As Tools For Genetic Screeningmentioning

confidence: 99%

Retroviral insertional mutagenesis: past, present and future

et al. 2005

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Retroviral insertion mutagenesis screens in mice are powerful tools for efficient identification of oncogenic mutations in an in vivo setting. Many oncogenes identified in these screens have also been shown to play a causal role in the development of human cancers. Sequencing and annotation of the mouse genome, along with recent improvements in insertion site cloning has greatly facilitated identification of oncogenic events in retrovirus-induced tumours. In this review, we discuss the features of retroviral insertion mutagenesis screens, covering the mechanisms by which retroviral insertions mutate cellular genes, the practical aspects of insertion site cloning, the identification and analysis of common insertion sites, and finally we address the potential for use of somatic insertional mutagens in the study of nonhaematopoietic and nonmammary tumour types.

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Section: Transforming Retroviruses As Tools For Genetic Screeningmentioning

confidence: 99%

Retroviral insertional mutagenesis: past, present and future

et al. 2005

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“…They decrease BCR/ABL mRNA and p210 BCR/ABL protein levels, inhibit growth and survival of BCR/ ABL expressing cell lines, and decrease tumorigenicity of BCR/ABL expressing cells in SCID mice (Lange, 1995;Lange et al, 1993Lange et al, , 1994Shore et al, 1993). However, ribozymes result in only imperfect cleavage of target mRNAs (James and Gibson, 1998).…”

Section: Antisense Strategiesmentioning

confidence: 99%

BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia

2002

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“…This top agar was left at 421C. NIH3T3 cells were transfected with pcDNA3-vector or pcDNA3 vector encoding Ga 12 QL (5 mg) along with or without STAT3DB (5 mg) were added using the calcium phosphate transfection method (Shore and Reddy, 1989). The transfected NIH3T3 cells (5 Â 10 4 cells in 100-200 ml of DMEM) were added into the top-agar mixture and uniformly overlayed on the bottom agar layer.…”

Section: Soft Agar Assaymentioning

confidence: 99%

“…Focus formation assay NIH3T3 cell focus formation assay was carried out as previously described (Shore and Reddy, 1989). The dominant negative, DNA-binding mutant of STAT3 (STAT3DB) was a generous gift from Dr E Premkumar Reddy (Fels Institute for Cancer Research, PA, USA).…”

Section: Immunoprecipitations and Western Blot Analysismentioning

confidence: 99%

Neoplastic transformation by the gep oncogene, Gα12, involves signaling by STAT3

2005

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Ga 12 , the a-subunit of G12, which has been referred to as the gep oncogene, stimulates mitogenic pathways in different cell types and readily induces neoplastic transformation of fibroblast cell lines. Recently, we have shown that the oncogenic pathway activated by Ga 12 involves the receptor tyrosine kinase platelet derived growth factor receptor-a (PDGFRa) and JAK3. In the present study, we demonstrate that the GTPase-deficient activated mutant of Ga 12 activates signal transducer and activator of transcription 3 (STAT3) via PDGFRa as well as JAK3. Here we show that Ga 12 stimulates the phosphorylation of STAT3 at both Tyrosine-705 and Serine-727 residues. Studies to delineate the mechanism by which Ga 12 stimulates STAT3 have indicated that the Tyrosine-705-phosphorylation of STAT3 involves the tyrosine kinases, Janus Kinase-3 as well as Src kinase, whereas the Serine-727 phosphorylation of STAT3 occurs via the receptor tyrosine kinase, PDGFRa and phosphatidylinositol 3-OH kinase pathway. Our results also indicate that the coexpression of the dominant negative, DNA binding mutant of STAT3 (STAT3DB) inhibits the foci formation as well as anchorage-independent growth of Ga 12 QL-transfectants, thereby establishing the critical role of STAT3 in Ga 12 QL-mediated neoplastic cell growth. The results presented here demonstrate, for the first time, the ability of Ga 12 to recruit multiple receptor-, nonreceptor-, and Ser/Thr kinases to stimulate STAT3-signaling to promote neoplastic transformation.

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Transforming pathways activated by the v-Abl tyrosine kinase

Cited by 37 publications

References 92 publications

Retroviral insertional mutagenesis: past, present and future

Retroviral insertional mutagenesis: past, present and future

BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia

Neoplastic transformation by the gep oncogene, Gα12, involves signaling by STAT3

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