C. Ponzetto - Academia.edu (original) (raw)

Papers by C. Ponzetto

Developmental Dynamics, 2004

The Pax3 and c-met genes are necessary for the development of tongue, diaphragm, and limb muscles... more The Pax3 and c-met genes are necessary for the development of tongue, diaphragm, and limb muscles. These hypaxial muscles derive from precursors that migrate out of the ventrolateral lip of the somites at occipital, cervical, and limb levels. In this work, we re-examined primary myogenesis in c-met signaling mutants using a skeletal muscle-specific lacZ transgene (Mlc3f-nlacZ-2E). This strategy allowed us to identify precisely the shoulder, limb, tongue, and dermal muscles that need Met for development and to confirm that the morphological structure of epaxial and body wall muscles was normal, even in the most severe c-met mutant. Surprisingly, however, X-gal staining showed that, in this mutant, hyoid arch-derived facial muscles were either reduced or absent, thus revealing that Met also contributes to the development of muscles in the head. Developmental Dynamics 231:582-591, 2004.

Journal of Neuroscience, 2006

. Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle a... more . Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle and survival. Here we show, by using three independent nestin Cre transgenic lines, that high levels of Cre recombinase expression into the nucleus of neuronal progenitors can compromise normal brain development. The transgenics analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase with a nuclear localization signal, and two nestin CreER T2 (Cre recombinase fused with a truncated estrogen receptor) mice lines with different levels of expression of a hybrid CreER T2 recombinase that translocates into the nucleus after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed reduced neuronal proliferation, increased aneuploidy and cell death, as well as defects in ependymal lining and lamination of the cortex, leading to microencephaly and to a form of communicating hydrocephalus. An essentially overlapping phenotype was observed in the two nestin CreER T2 transgenic lines after tamoxifen mediated-CreER T2 translocation into the nucleus. Neither tamoxifen-treated wild-type nor nestin CreER T2 oil-treated control mice displayed these defects. These results indicate that some forms of hydrocephalus may derive from a defect in neuronal precursors proliferation. Furthermore, they underscore the potential risks for developmental studies of high levels of nuclear Cre in neurogenic cells.

Blood, 1988

By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and b... more By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and blast crisis) or lymphoid and myeloid Philadelphia chromosome (Ph') positive acute leukemias, we have investigated the relationship between the molecular defect on the Ph' chromosome and the associated hematologic phenotype. As expected, approximately half of the Ph' positive acute leukemias showed a breakpoint on chromosome 22 falling outside the "breakpoint cluster region" (bcr) known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic phase also showed rearrangements falling outside the bcr region. In two of these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb upstream to the bcr region. In another case, the breakpoint was located approximately 16 kb downstream to bcr. In the remaining four cases, the precise position of the rearrangement could not be localized with the available bcr probes. DNAs from patients with CML blast...

PLoS ONE, 2008

Background: Osteosarcoma (OSA) is lethal when metastatic after chemotherapy and/or surgical treat... more Background: Osteosarcoma (OSA) is lethal when metastatic after chemotherapy and/or surgical treatment. Thus animal models are necessary to study the OSA metastatic spread and to validate novel therapies able to control the systemic disease. We report the development of a syngeneic (Balb/c) murine OSA model, using a cell line derived from a spontaneous murine tumor.

European Journal of Cancer, 2008

Bortezomib Proteasome Novel cancer therapies A B S T R A C T Rhabdomyosarcoma (RMS) is the most c... more Bortezomib Proteasome Novel cancer therapies A B S T R A C T Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, divided into two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). To explore the possibility that the proteasome could be a target of therapeutic value in rhabdomyosarcoma, we treated several RMS cell lines with the proteasome inhibitor bortezomib (Velcade or PS-341) at a concentration of 13-26 nM. RMS cells showed high sensitivity to the drug, whereas no toxic effect was observed in primary human myoblasts. In both ERMS and ARMS cells bortezomib promoted apoptosis, activation of caspase 3 and 7 and induced a dose-dependent reduction of anchorage-independent growth. Furthermore, bortezomib induced activation of the stress response, cell cycle arrest and the reduction of NF-jB transcriptional activity. Finally, bortezomib decreased tumour growth and impaired cells viability, proliferation and angiogenesis in a xenograft model of RMS. In conclusion, our data indicate that bortezomib could represent a novel drug against RMS tumours.

Cell, 1994

Signaling by tyrosine kinase receptors is mediated by selective interactions between individual S... more Signaling by tyrosine kinase receptors is mediated by selective interactions between individual Src homology 2 (SH2) domains of cytoplasmic effectors and specific phosphotyrosine residues in the activated receptor. Here, we report the existence in the hepatocyte growth factor/scatter factor (HGF/SF) receptor of a multifunctional docking site made of the tandemly arranged degenerate sequence YVH/NV. Phosphorylation of this site mediates intermediate- to high-affinity interactions with multiple SH2-containing signal transducers, including phosphatidylinositol 3-kinase, phospholipase C gamma, pp60c-src, and the GRB-2-Sos complex. Mutation of the two tyrosines results in loss of biological function, as shown by abrogation of the transforming activity in the oncogenic counterpart of the receptor. The same bidentate motif is conserved in the evolutionarily related receptors Sea and Ron, suggesting that in all members of the HGF/SF receptor family, signal transduction is channeled through a multifunctional binding site.

Cancer Genetics and Cytogenetics, 1992

MKN 45 is a poorly differentiated gastric carcinoma cell line from which the subclone GTL 16 was ... more MKN 45 is a poorly differentiated gastric carcinoma cell line from which the subclone GTL 16 was obtained. Both lines carry an amplification unit derived from chromosome 7 sequences and containing an activated c-met oncogene. Karyotypic analysis showed that GTL 16 derived from a subclone of MKN 45 after endoreduplication. Several clonal abnormalities are evident in both lines; some are frequently observed in gastrointestinal tumors (loss of 17p and monosomy 18). Other consistent anomalies include 6q-, t(8;10) and t(5;8), and inv(16). A marker chromosome (M1), which was previously shown to contain the c-met amplification unit, is constantly duplicated in all GTL 16 metaphases; in contrast, most unidentified markers are retained in only a single copy in GTL 16 cells. These data are in agreement with the hypothesis that the c-met oncogene activation in these gastric cancer cell lines might be related to a gene dosage effect.

Cancer Genetics and Cytogenetics, 1991

British Journal of Haematology, 1998

Blood, 2006

Anaplastic large-cell lymphomas (ALCLs) carry chromosome translocations in which the anaplastic l... more Anaplastic large-cell lymphomas (ALCLs) carry chromosome translocations in which the anaplastic lymphoma kinase (ALK) gene is fused to several partners, most frequently, the NPM1 gene. We have demonstrated that the constitutive activation of ALK fusion proteins results in cellular transformation and lymphoid neoplasia. Herein, we specifically downregulated ALK protein expression by using small hairpin RNA (shRNA) targeting a sequence coding for the catalytic domain of ALK. The ablation of ALK leads to the down-modulation of known ALK downstream effectors, cell growth arrest, and reversion of the transformed phenotype of ALK ؉ mouse embryonic fibroblasts in vitro and in vivo. In human ALCL cells lentiviral-mediated ALK knock-down leads to G 1 cell-cycle arrest and apoptosis in vitro and tumor growth inhibition and regression in vivo. Using a specific approach we have demonstrated that the survival and growth of ALK ؉ ALCLs are strictly dependent on ALK activation and signaling. Therefore, ALK is a viable target for therapeutic intervention and its inactivation might represent a pivotal approach for the treatment of ALK lymphomas and other ALK-dependent human tumors.

Abstract The biological effects of hepatocyte growth factor/scatter factor are mediated by autoph... more Abstract The biological effects of hepatocyte growth factor/scatter factor are mediated by autophosphorylation of its receptor, the Met tyrosine kinase, on two carboxyl-terminal tyrosines. These phosphotyrosines (Y 1349 VHVNATY 1356 VNV) are multifunctional ...

Cellular and Molecular Life Sciences, 2014

Your article is protected by copyright and all rights are held exclusively by Springer Basel. Thi... more Your article is protected by copyright and all rights are held exclusively by Springer Basel. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".