Tandem orientation of the inter-α-trypsin inhibitor heavy chain H1 and H3 genes

Diarra‐Mehrpour, Maryam; Bourguignon, Jeannette; Sarafan, Nasrin; Bost, Fréd́eric; Sesboüé, Richard; Muschio-Bonnet, F; Martin, Josiane

doi:10.1016/0167-4781(94)90087-6

Cited by 11 publications

(11 citation statements)

References 17 publications

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“…It is clear from this study that these genes occur as single copies closely linked in a 45-kb in the order of 5Ј-ITIH1-ITIH3-ITIH4-3Ј. The tight clustering of the three genes is reminiscent of that seen in a number of eukaryotic gene families that have arisen by duplication and divergence from an ancestral gene (34). Based on the amino acid and nucleotide sequence homologies among the three ITI genes as well as on similarities of the exon/intron domains, a possible mechanism for the generation of the ITIH1, ITIH3, and ITIH4 genes is proposed in Fig.…”

Section: Discussionmentioning

confidence: 70%

“…We also determined the complete sequence of the fragment containing the last exon of ITIH1 and the first exon of ITIH3 (34). To determine whether the putative promoter region of ITIH3 is functional, we now constructed a series of 5Ј deletion mutants extending from Ϫ2928 toward the transcription start site (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For DNase footprinting, the HG H1/H3 clone described in Ref. 34 was digested with SalI, filled in with Klenow enzyme (Boehringer Mannheim), in a buffer containing 50 mM Tris-HCl, pH 8.0, 10 mM MgCl 2, 1 mM dATP, 1 mM dTTP, 10 mM dGTP (Boehringer Mannheim), and 10 l of [␣-…”

Section: Screening Of the Human Genomic Library-10mentioning

confidence: 99%

“…gene also spans 14 kb and is composed of 24 exons (33). The ITIH1 and ITIH3 genes are tandemly organized and separated by 2.7 kb (34). These genes are the acute-phase genes that are transcriptionally regulated in a different manner under the influence of interleukin-6 (35).…”

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confidence: 99%

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Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Diarra‐Mehrpour

Sarafan

Bourguignon

et al. 1998

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Screening Of the Human Genomic Library-10mentioning

confidence: 99%

mentioning

confidence: 99%

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Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Diarra‐Mehrpour

Sarafan

Bourguignon

et al. 1998

Journal of Biological Chemistry

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“…Such a difference could result from the strong homology of ITI-H1 and -H3 chains. 30,31 The absence of effect on primary tumor growth contrasting with the decrease of metastases number (Fig. 5b) implies that ITI-H1 and -H3 chains interfere specifically at least with 1 step of the metastatic process.…”

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confidence: 96%

Inhibition of tumor growth and metastatic spreading by overexpression of inter‐alpha‐trypsin inhibitor family chains

Paris

Sesboüé

Delpech³

et al. 2002

Intl Journal of Cancer

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The inter-␣ trypsin inhibitor (ITI) family is a group of proteins built up from different combinations of 1 light chain (ITI-L) and 3 highly homologous heavy chains (ITI-H1, -H2 and -H3). To investigate a potential role of the ITI family chains in cancer and metastasis spreading, we engineered human H460M cell lines expressing both the green fluorescent protein (GFP) and one of these chains. These clones were subcutaneously injected in athymic nude mice, and lung metastasis number and primary tumor weight were determined after 28 days. Expression of the ITI-L chain considerably decreased tumor weight and fluorescent lung metastasis number. ITI-H1 and ITI-H3 chain expression induced a significant decrease of metastasis number, whereas no decrease of tumor weight could be detected. Key words: inter-␣-trypsin inhibitor; green fluorescent protein; spontaneous lung metastases; primary tumorInhibition of the metastatic process represents an important challenge in cancer treatment, and potential therapeutic approaches include the inhibition of matrix metalloproteinases, 1 of the vascular endothelial cell growth factor (VEGF) pathway 2 or the activation of metastasis suppressor genes. 3 Although most of the molecules involved in the metastatic process have not been identified, it is now established that alteration of the extracellular matrix (ECM) plays an important role in cell migration and metastasis. 4 The major ECM component, hyaluronic acid (HA), is organized as a complex network of macromolecules involving hyaluronic acidbinding proteins (HABP) 5 and the ITI family. The most of ITI members are composed of variable associations of light (ITI-L) and heavy chains (ITI-H1, -H2, -H3), encoded by 4 different genes on 3 chromosomes, 6 -9 giving rise to a series of proteins covalently linked by a glycosaminoglycan 10 and differing in their chain composition. 11 Although the binding of ITI to HA is known for a long time, 12 involvement of heavy chains in this linkage was only recently demonstrated 13-15 together with a major role in the ECM stability of the mouse cumulus oocyte complex. 16 The ITI-L chain mRNA encodes 2 tandemly arranged proteins that separate after proteolytic cleavage: the ␣ 1 -microglobulin (␣ 1 m) that belongs to the lipocalin superfamily 17 and the bikunin that contains 2 Kunitz inhibitory domains responsible for the protease inhibitory activity of ITI molecules. 18 Different studies have suggested a potential antimetastatic effect of bikunin: (i) it inhibits in vitro tumor cell receptor-bound plasmin 19 and the invasiveness of malignant cells; 20,21 and (ii) injections of human purified bikunin efficiently reduced the number of metastases produced by the murine 3LL cell line. 22 We have therefore analyzed in the present study the antimetastatic effect of the different ITI chains using a model of fluorescent spontaneous lung metastases. 23 MATERIAL AND METHODS Cells lines and cultureThe H460M cell line, initially derived from the parental NCI-H460 cell line established from a large-cell carcinoma o...

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Frequency and prognostic evaluation of 3p21‐22 allelic losses in non‐small‐cell lung cancer

Thiberville¹,

Bourguignon²,

Metayer³

et al. 1995

Intl Journal of Cancer

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Previous loss of heterozygosity (LOH) studies of chromosome 3p loci have displayed a 60% deletion frequency in non-small-cell lung cancers (NSCLC), as opposed to small-cell lung cancers, in which the 3p deletion is consistently found. However, the high stromal-cell admixture found in NSCLC and the use of the Southern-blot method lead to under-evaluation of this frequency. In this study, we used a very precise microdissection technique followed by PCR amplification of 6 3p21-22 polymorphic genomic sequences to analyze LOH in 86 NSCLC and in normal adjacent tissue. We found the sensitivity of the microdissection-PCR-based LOH technique higher than the sensitivity of the Southern-blot technique: 87% of the squamous-cell carcinomas and 84% of the large-cell undifferentiated carcinomas showed a clear LOH for a 3p21-22 locus. All doubly informative cases but 4 showed concordant deletion at all 3p21-22 loci. The analysis of 3p microsatellite sequences displayed only 2 cases of genomic instability, one of them also displaying features of tumoral heterogeneity as regards the instability genotype. Four carcinomas in situ adjacent to these NSCLC showed the same allelic profile as the invasive tumors. The only prognostic factors in this study were the disease stage and histology. The 3p21-22 deletion was not related to the stage of the disease and did not appear to be a significant prognostic factor of survival. 3p21 loss appears, so far, to be the most frequent and the earliest genetic alteration described in NSCLC, but does not seem to carry significant prognostic information in invasive tumors.

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Tandem orientation of the inter-α-trypsin inhibitor heavy chain H1 and H3 genes

Cited by 11 publications

References 17 publications

Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Inhibition of tumor growth and metastatic spreading by overexpression of inter‐alpha‐trypsin inhibitor family chains

Frequency and prognostic evaluation of 3p21‐22 allelic losses in non‐small‐cell lung cancer

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