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L De Gregorio

Publications and source records attributed to L De Gregorio.

33 records · Page 2Linked to original sources
PubMed1996

The FHIT gene 3p14.2 is abnormal in lung cancer.

To determine the role of the FHIT gene, which encompasses the fragile site at 3p14.2, we analyzed 59 tumors of the small cell and non-small cell type by reverse transcription of FHIT mRNA, followed by PCR amplification and sequencing of products. Allelic losses affecting the gene were evaluated by microsatellite polymorphism analysis and genomic alterations by hybridization using cDNA and genomic probes. Small cell lung tumors (80%) and non-small cell lung cancers (40%) showed abnormalities in RNA transcripts of FHIT, and 76% of the tumors exhibited loss of FHIT alleles. Abnormal lung tumor transcripts lack two or more exons of the FHIT gene. Small cell lung cancer tumors and cell lines were analyzed by Southern blotting and showed rearranged BamHI fragments. These data suggest a critical role of the FHIT gene in lung carcinogenesis.

Amino Acid Sequence↗
PubMed1996

Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites.

Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the "pentraxin family signature." Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.

3T3 Cells↗
PubMed1996

The placenta growth factor gene of the mouse.

Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) are angiogenic factors containing the 8-cysteine motif of platelet-derived growth factor (PDGF). Both PlGF and VEGF are mitogens for endothelial cells in vitro and promote neoangiogenesis in vivo. In addition, PlGF strongly potentiates the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. We have now isolated the cDNA coding for mouse Plgf by screening a mouse heart cDNA library with the human PlGF sequence as probe. The human PlGF protein has two forms, PlGF-1 and PlGF-2, that arise from alternative splicing of a single gene mapping on Chromosome (Chr) 14; the isolated mouse Plgf cDNA encodes the longer of these two forms (PlGF-2). We show that the mouse Plgf-2 mRNA is the only transcript present in the normal tissues analyzed. Mouse Plgf-2 is a 158-amino-acid-long protein that shows 78% similarity (65% identity) to the human PlGF-2. Computer analysis reveals a putative signal peptide and three probable N-glycosylation sites, two of which are also conserved in human PlGF. The mouse Plgf gene was isolated and characterized; the gene is encoded by 7 exons spanning a 13-kb DNA interval. Finally, we have mapped the mouse Plgf gene to Chr 12, one cM from D12Mit5, and the human PlGF gene to 14q24, using both FISH and genetic crosses.

Animals↗
PubMed1996

Differentiation dependent expression in muscle cells of ZT3, a novel zinc finger factor differentially expressed in embryonic and adult tissues.

ZT3, isolated from a murine muscle cell cDNA library by a low-stringency hybridization, encodes a zinc finger domain containing factor with a transcript of 5.0 kb. A 3' 2.5 kb partial nucleotide sequence contains an ORF of 1.5 kb where 17 canonical C2H2 zinc finger domains organized in tandem were identified. It maps on mouse chromosome 11, close to two mutations which affect skeletal formation. ZT3 expression depends upon differentiation of myogenic cells in culture, since it is upregulated with myogenin and inhibited in scr-transfected C2C12 cells. ZT3 is not expressed in NIH3T3 or C3H10T1/2 fibroblasts, but is induced when fibroblasts are myogenically converted by transfection with the muscle regulatory genes (MRFs). Its expression is also upregulated in the rhabdomyosarcoma cell line RD induced to myogenic differentiation by TPA treatment. In postimplantation embryos, ZT3 is diffusely expressed but higher expression is detectable in the neural tube and encephalic vesicles, in the somites and, at a high level, in the limb buds as they form. During further development ZT3 is expressed in many tissues of neuroectodermal and mesodermal origin, but its expression decreases during fetal development and in the adult it is restricted to skeletal and cardiac muscle and to spleen. This pattern of expression suggests a possible role played by ZT3 in differentiating skeletal muscle. Its expression in other tissues is compatible with the suggestion that members of this class of DNA-binding factors play different roles during post-implantation development and in the adult life.

3T3 Cells↗
PubMed1996

Genetic mapping of a pulmonary adenoma resistance (Par1) in mouse.

Lung cancer, a major cause of death in the Western world, has a poor prognosis. So far, therapeutic strategies have had only a limited effect. Lung cancer risk is strongly associated with cigarette smoking and lung cancer pedigrees are rare. However, a possible polygenic nature of inherited predisposition to this cancer has been envisaged. Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an important tool for the dissection of the genetics of this complex disease. The A/J strain carries the pulmonary adenoma susceptibility 1 (Pas1) locus and develops many lung tumours. We have mapped the M. spretus-derived locus that strongly resists the lung tumorigenesis in Pas1/+ mice. This locus, pulmonary adenoma resistance 1 (Par1) maps to mouse chromosome 11, near the Rara locus, with a lod score of 5.3. In Pas1/+ mice Par1 accounts for 23% of the phenotypic variance and 10 fold reduction in total tumour volume. These results provide evidence for a major resistance locus affecting the expression of an inherited predisposition to lung cancer.

Adenoma↗
PubMed1995

Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions.

Patients with a primary cancer in the lung or in the upper aerodigestive tract have an increased risk of developing synchronous or metachronous second primary lung tumors. This phenomenon has been related to the chronic exposure of the bronchial tree to carcinogens through a so-called "field cancerization" process. This study was designed to investigate at the somatic level the genetic basis of the field cancerization effect in patients having multiple simultaneous neoplastic and preneoplastic lesions of the lung. The pattern of specific genetic changes occurring with high frequency and in early stages of lung carcinogenesis including p53 mutations, deletions of chromosome 3p, and K-ras mutations, was investigated by immunocytochemical, cytogenetic, and molecular approaches in 11 synchronous lesions of five patients with multiple lung cancers. Different genetic lesions were observed in all of the pathological specimens analyzed from each patient. The pattern of these changes was different both in topographically distant or adjacent lesions and in tumors with the same histopathological diagnosis supporting their independent origin. The present data provide further evidence of the clinical relevance of the field cancerization process, and support the use of genetic markers in the differential diagnosis of recurrence or metastasis versus second primaries of the lung.

Adenocarcinoma↗
PubMed1995

Analysis of loss of heterozygosity in murine hepatocellular tumors.

Because allelotype analysis of tumors has been important in the identification of new tumor suppressor genes, here we studied loss of heterozygosity (LOH) in a well-defined animal experimental system. We analyzed spontaneous liver tumors from C3HHc x C57BL/6J (B6C3F1) mice and urethane-induced hepatocellular tumors from (C3H/He x Mus spretus) x C57BL/6JBy (HSB) interspecific mice. A total of 95 different genetic markers were tested: 13 in 24 B6C3F1 tumors, 76 in 58 HSB tumors, and six in both groups. Minisatellite finger-printing analysis detected one case of LOH and less than 1% genomic rearrangements in polymorphic and nonpolymorphic bands, respectively. There were no changes at hepatocellular susceptibility loci or at markers homologous to loci frequently lost in human hepatocellular carcinomas. Therefore, our results suggest that LOH and genomic rearrangements are uncommon in mouse hepatocellular tumors.

Alleles↗
PubMed1995

Mapping of the Hmg1 gene and of seven related sequences in the mouse.

The High Mobility Group 1 protein (HMG1) is an abundant and highly conserved chromosomal protein. Mouse HMG1 is encoded by the Hmg1 gene, containing four introns, but the murine genome contains many related sequences that are mostly retrotransposed pseudogenes. By using an interspecific cross, we have mapped the functional Hmg1 gene on mouse Chromosome (Chr) 5 and seven Hmg1-related sequences on Chrs 6, 8, 17, 18, and X.

Animals↗
PubMed1995

Genetics of liver tumor susceptibility in mice.

A good experimental model of genetic predisposition to hepatocellular tumors is the murine strain C3H. These tumors share morphologic similarities with human hepatocellular tumors. After a treatment with a single small dose of chemical carcinogen, the C3H mice show a high susceptibility to the growth of hepatocellular neoplastic lesions, that reach a volume > 100-fold as compared to the corresponding lesions of genetically resistant strains. Genetic linkage analysis experiments were conducted in 2 different crosses, with the C3H as one of the parental strains, and the other parental strains being represented by mice genetically resistant to hepatocarcinogenesis (A/J, M. spretus). Six different regions, on chromosomes 2, 5, 7, 8, 12, and 19 showed a significant linkage with hepatocellular tumor development. These results provide the genetic basis for the strain variations seen in susceptibility to hepatocarcinogenesis, indicating polygenic inheritance of this trait.

Animals↗
PubMed1994

Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice.

The C3H/He mouse represents a good experimental model of genetic predisposition to hepatocellular tumor development. We analyzed an interspecific test-cross population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice, typed with 222 genetic markers to locate precisely the hepatocellular tumor susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a significant linkage with hepatocellular tumor development, as indicated by different quantitative indexes estimating liver tumor size. Liver tumor frequency was not genetically controlled. These loci are different from three other Hcs loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed with the resistant laboratory strain A/J. The present result indicates a multigenic model of inheritance for hepatocellular tumor susceptibility.

Animals↗
PubMed1994

Comparative mapping of the actin-binding protein 280 genes in human and mouse.

Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, we have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. We mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, we mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7.

Animals↗
PubMed1994

Expression in lung tumors and genetic mapping of the novel murine protein kinase C eta.

Protein kinase C eta (nPKC eta) is a member of the protein kinase C family with a unique tissue distribution in skin and lung. We analyzed nPKC eta expression in normal murine lung and in 36 lung tumors induced by urethane in AC3 F1 and F2 mice. The nPKC eta-related transcript was present at fivefold to tenfold lower levels in tumors than in normal lung controls. We mapped two distinct loci for nPKC eta on murine chromosome 12, using linkage analysis in an interspecific test cross. The results indicate that the mouse Pkcn-rs1 and Pkcn-rs2 loci were about 30 cM from the centromere and about 2 cM from each other.

Animals↗