Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration

Benelli, Roberto; Peissel, Bernard; Manenti, Giacomo; Gariboldi, Manuela; Vanzetto, Christian; Albini, Adriana; Dragani, Tommaso A.

doi:10.1038/sj.onc.1207088

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Consistent with our results, overexpression of CCL2 or ANXA1 in other systems promotes or inhibits cell migration, respectively (Cambien et al, 2001;Parente and Solito, 2004). Thus, alteration of ANXA1, CCL2, FN1, and TFF3 gene expression may reflect a mechanism responsible for the allele-specific cell adhesion and migration effects of the mouse Pthlh gene (Benelli et al, 2003). ANXA1 (Parente and Solito, 2004), CCL2 (Maus et al, 2003), and TFF3 are also involved in the modulation of the inflammatory response and may represent targets of the parathyroid hormone-related protein (PTHrP), which can modulate the inflammatory response in several conditions (Funk, 2001).…”

Section: Gene Expression Profiles Point To Functional Allelic Differesupporting

confidence: 77%

“…Genes showing the greatest differences in expression in the dye-swap experiment were selected for analysis by gene profiling, of 32 clones (isolated from the original variant or left non-transfected were maintained as described (Manenti et al, 2000;Benelli et al, 2003). Three independent preparations of each transfectant were grown and used for microarray analysis.…”

Section: Microarray Results Correlate With Krt-pcr Analysismentioning

confidence: 99%

“…The functions of the three alleles of the candidate mouse cancer modifier gene Pthlh (Manenti et al, 2000) are known, with Pthlh Pro allele linked to genetic susceptibility to two-stage skin carcinogenesis and increased cell migration in vitro, whereas Pthlh Thr and Pthlh SerAspTyr are linked with genetic resistance to skin carcinogenesis and with reduced cell migration of transfected cells in vitro (Manenti et al, 2000;Nagase et al, 2001;Benelli et al, 2003). We found that specific mRNA expression profiles are associated with the three Pthlh alleles, with a clustering that is associated with the biological activities of the alleles.…”

Section: Gene Expression Profiles Point To Functional Allelic Differementioning

confidence: 99%

“…The evolutionarily distant mouse species Mus spretus carries an additional allele (Pthlh SerAspTyr ) and these mice are genetically resistant to skin carcinogenesis (Nagase et al, 2001). In vitro effects of Pthlh alleles on cellular morphology, adhesion efficiency and migration capability, as well as growth of the transfected human squamous cell carcinoma cell line NCI-H520 in nude mice, correlate with in vivo susceptibility/resistance to skin tumorigenesis of the mouse strains and lines carrying these alleles (Manenti et al, 2000;Benelli et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells

et al. 2006

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Section: Gene Expression Profiles Point To Functional Allelic Differesupporting

confidence: 77%

Section: Microarray Results Correlate With Krt-pcr Analysismentioning

confidence: 99%

Section: Gene Expression Profiles Point To Functional Allelic Differementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells

et al. 2006

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“…After 1 h, all coating solutions were removed, and HUVEC (20,000 cells per well) were plated in SFM, in the presence or absence of 1 M IMO. After incubation, cells were analyzed as described (37).…”

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confidence: 99%

TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts

Damiano¹,

Caputo²,

Garofalo³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Synthetic agonists of Toll-like receptor 9 (TLR9), a class of agents that induce specific immune response, exhibit antitumor activity and are currently being investigated in cancer patients. Intriguingly, their mechanisms of action on tumor growth and angiogenesis are still incompletely understood. We recently discovered that a synthetic agonist of TLR9, immune modulatory oligonucleotide (IMO), acts by impairing epidermal growth factor receptor (EGFR) signaling and potently synergizes with anti-EGFR antibody cetuximab in GEO human colon cancer xenografts, whereas it is ineffective in VEGF-overexpressing cetuximab-resistant GEO cetuximab-resistant (GEO-CR) tumors. VEGF is activated by EGFR, and its overexpression causes resistance to EGFR inhibitors. Therefore, we used IMO and the anti-VEGF antibody bevacizumab as tools to study IMO's role on EGFR and angiogenesis and to explore its therapeutic potential in GEO, LS174T, and GEO-CR cancer xenografts. We found that IMO enhances the antibody-dependent cell-mediated cytotoxicity (ADCC) activity of cetuximab, that bevacizumab has no ADCC, and IMO is unable to enhance it. Nevertheless, the IMO-plus-bevacizumab combination synergistically inhibits the growth of GEO and LS174T as well as of GEO-CR tumors, preceded by inhibition of signaling protein expression, microvessel formation, and human, but not murine, VEGF secretion. Moreover, IMO inhibited the growth, adhesion, migration, and capillary formation of VEGF-stimulated endothelial cells. The antitumor activity was irrespective of the TLR9 expression on tumor cells. These studies demonstrate that synthetic agonists of TLR9 interfere with growth and angiogenesis also by EGFR-and ADCCindependent mechanisms affecting endothelial cell functions and provide a strong rationale to combine IMO with bevacizumab and EGFR inhibitory drugs in colon cancer patients.angiogenesis ͉ cancer therapy ͉ growth factor receptors

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Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross

Norgard

Lawson²,

Pletscher³

et al. 2010

Mamm Genome

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Previous studies on the LG,SM advanced intercross line have identified ~40 quantitative trait loci (QTL) for long bone (humerus, ulna, femur, and tibia) lengths. In this study, long bone length QTL were fine-mapped in the F34 generation (n=1,424) of the LG,SM advanced intercross. Environmental effects were assessed by dividing the population by sex between high fat and low fat diet, producing eight sex/diet cohorts. We identified 145 individual bone length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from previous studies, 35 were new traits significant at previously identified loci, and 41 were novel QTL. Many QTL affected only a subset of the population based on sex and/or diet. Eight of ten known skeletal growth genes were up-regulated in 3-week-old LG/J male proximal tibial growth plates, relative to SM/J. The sequences of parental strains LG/J and SM/J indicated the presence of over half a million polymorphisms in the confidence intervals of these 45 QTL. We examined 526 polymorphisms and found that 97 represented radical changes to amino acid composition while 40 were predicted to be deleterious to protein function. Additional experimentation is required to understand how changes in gene regulation or protein function can alter the genetic architecture and interact with the environment to produce phenotypic variation.

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Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration

Cited by 8 publications

References 26 publications

Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells

Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells

TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts

Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross

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