[go: up one dir, main page]

WO2000032819A1 - Methodes de diagnostic, de pronostic et de traitement des maladies associees a la metalloproteinase matricielle 1 via un polymorphisme nucleotidique simple de cette metalloproteinase matricielle 1 - Google Patents

Methodes de diagnostic, de pronostic et de traitement des maladies associees a la metalloproteinase matricielle 1 via un polymorphisme nucleotidique simple de cette metalloproteinase matricielle 1 Download PDF

Info

Publication number
WO2000032819A1
WO2000032819A1 PCT/US1999/026610 US9926610W WO0032819A1 WO 2000032819 A1 WO2000032819 A1 WO 2000032819A1 US 9926610 W US9926610 W US 9926610W WO 0032819 A1 WO0032819 A1 WO 0032819A1
Authority
WO
WIPO (PCT)
Prior art keywords
matrix metalloproteinase
mmp
single nucleotide
nucleotide polymorphism
snp
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1999/026610
Other languages
English (en)
Inventor
Constance E. Brinckerhoff
Joni L. Rutter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dartmouth College
Original Assignee
Dartmouth College
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dartmouth College filed Critical Dartmouth College
Priority to US09/856,749 priority Critical patent/US7033756B1/en
Publication of WO2000032819A1 publication Critical patent/WO2000032819A1/fr
Anticipated expiration legal-status Critical
Priority to US11/408,202 priority patent/US7473774B2/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • MMPs matrix metalloproteinases
  • MMP-1 is the most ubiquitously expressed interstitial collagenase, thereby assigning it a prominent role in collagen degradation.
  • Overexpression of MMP-1 is associated with several pathological conditions, including the irreversible degradation of cartilage, tendon, and bone in arthritis
  • MMP-1 has been suggested to be due to the juxtaposition of transcription factor binding sites within the promoter of this gene and to the cooperativity among the factors that bind these sites (Buttice et al . Oncogene 13:2297-2306, 1996; Basuyaux et al . J. Biol . Chem. 272:26188- 26195, 1997; Gutman, A. and Waslyk, B. EMBO J. 9:2241-2246, 1990; Benbow, U. and Brinckerhoff, C.E. Matrix Biol. 15:519- 526, 1997) .
  • MMP-1 Most normal cells express modest, but detectable, levels of MMP-1 constitutively, and this expression increases substantially in the presence of cytokines or growth factors (Vincenti et al . Crit. Rev. Eukaryotic Gene Expr. 6:391-411, 1996; Rutter et al . J. Cell Biochem. 66:322-336, 1997; Aho et al. Eur. J. Biochem. 247:503-510, 1997; Delany, A.M. and Brinckerhoff, C.E. J. Cell Biochem. 50:400-410, 1992). However, A2058 melanoma cells constitutively express high levels of MMP-1 (Templeton et al. Cancer Res.
  • An object of the present invention is to provide a method of diagnosing MMP-1 related diseases in a patient which comprises detecting m a patient MMP-1 containing an Ets transcription factor binding site single nucleotide polymorphism (MMP-1 EBS-SNP) .
  • MMP-1 EBS-SNP Ets transcription factor binding site single nucleotide polymorphism
  • SNPs single nucleotide polymorphisms
  • MMP-1 EBS-SNP This SNP, referred to herein as MMP-1 EBS-SNP, was examined in detail.
  • HFS normal foreskin fibroblasts
  • A2058 melanoma cells expressed higher levels.
  • PCR polymerase chain reaction
  • detection of the MMP-1 EBS-SNP in a patient provides a useful means for diagnosing MMP-1 related diseases.
  • Detection of MMP-1 EBS-SNP in a patient is indicative of the patient suffering from a disease relating to overexpression of the MMP-1 enzyme. Detection of this SNP can be performed m accordance with well known techniques including, but not limited to, PCR as described herein.
  • MMP-1 EBS-SNP which is indicative of enhanced ability to degrade collagen types I, II and III, in tumor cells of a patient serves as a useful prognostic marker in assessing the invasiveness of a particular tumor.
  • This prognostic marker is thus useful in determining various treatment regimes expected to be most successful in individual patients.
  • Means for detecting MMP-1 EBS-SNP in a patient sample for diagnosing and/or prognosticating MMP-1 related diseases can be incorporated into a kit for easy use by a laboratory technician.
  • the kit can comprise PCR primers such as those described in Example 5 herein which flank the MMP-1 EBS SNP.
  • the kit may also comprise dGTP, dATP, dTTP, and dCTP; Taq DNA polymerase; and ⁇ (32)P-dCTP.
  • Kits of the present invention may also comprise positive and negative control samples.
  • HFF human foreskin fibroblasts
  • a 4.3-kb MMP-1 promoter DNA fragment containing only 1G at -1607 bp was described by Rutter et al . J. Cell Biochem. 66:322-336, 1997.
  • Primers were made to amplify the endogenous promoter from the A2058 cells (-4008 bp to -3988 bp sense primer: 5 ' -GTGGAAGCTTACACCTATAATCCCAACACTC-3 ' (SEQ ID NO: 4) and -511 bp to -543 bp antisense primer: 5'- CTGCCTGGTACCCTATTGCGATAGCACCATGGC-3' (SEQ ID NO: 5).
  • Transient transfections were performed in triplicate in accordance with procedures described by Rutter et al . J. Cell Biochem. 66:322-336, 1997 with the LipofectAMINE PLUS reagent (Life Technologies, Inc.) using 2 ⁇ g of the chimeric MMP-1 promoter/reporter plasmids, 5 ⁇ l of the PLUS reagent, and 5 ⁇ l of LipofectAMINE . Luciferase activity is reported as RLUs. Hirt's analyses were performed and normalized to RLUs to control for any variations in transfection efficiency. Statistics were performed using the InStat Program (GraphPad Software) using the Welch's alternate t test, a modification of the unpaired t test.
  • Extracts of nuclear proteins were prepared, and EMSAs were performed as described by Schroen, D.L. and Brinckerhoff, C.E. J. Cell Physiol. 169:320-332, 1996, with 1 x 10 5 cpm of ⁇ 32 P-ATP end-labeled oligo incubated with nuclear extract (5 ⁇ g) and/or recombinants ETS-1 protein (2 ⁇ M) and c-JUN protein (1 ⁇ g; Promega) . The samples were subjected to 5% PAGE at 150 V, dried, and autoradiographed .
  • Oligos used for EMSAs were 1G sense, 5 ' -AAATAATTAGAAAGATATGACTTATCTCAAATCAA-3 ' (SEQ ID NO: 6); 2 G sense, 5 ' -AAATAATTAGAAAGGATATGACTTATCTCAAATCAA: (SEQ ID NO: 7) -88/-73 sense, 5'- TTCATTGTTAATCAAGAGGATGTTATAAAGCATGAGTCACACCCTCAGCTT-3 ' (SEQ ID NO: 8) .
  • the -88/-73 oligo spans the region -110 to -61 bp and includes the locations within the oligo that correspond to the proximal PEA3/AP-1 sites at the -88/-73, respectively.
  • Primers that flank the SNP in MMP-1 were used for PCR amplification (sense primer, 5 ' -GTTATGCCACTTAGATGAGG-3 ' (SEQ ID NO: 9); antisense primer 5 ' -TTCCTCCCCTTATGGATTCC-3 ' (SEQ ID NO: 10)).
  • a typical reaction consisted of -20 ng of DNA template; 0.2 mM dGTP, dATP, and dTTP, 2.5 ⁇ M dCTP; 10 x buffer and Taq DNA polymerase (Sigma Chemical Co.); and ⁇ (32)P-dCTP (DuPont/NEN) .
  • Reactions were PCR amplified (MJ Research PTC100 THERMOCYCLER) in 25 cycles (4 minutes at 94°C; 45 seconds at 94°C, 45 seconds at 58°C, and 45 seconds at 72°C; followed by a brief extension (10 minutes) at 72°C) .
  • the reactions (2.5 ⁇ l) were mixed with 10 X loading buffer and denatured for 2 minutes at 80°C. Samples were loaded onto an 8% denaturing PAGE and electrophoresed for 3 hours. Gels were dried and autoradiographed for approximately 15 minutes. Control samples generated from the plasmid clones were loaded on each gel for accurate scoring of the alleles. Statistics were calculated using the InStat Program (GraphPad Software) and were based on the percentage of the total number tested.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne des méthodes et des kits de diagnostic et de pronostic de maladies associées à la métalloprotéinase 1 matricielle, lesquelles méthodes consistent à détecter un polymorphisme nucléotidique simple dans le promoteur du gène. L'invention concerne également des méthodes d'identification d'agents inhibant la liaison des facteurs de transcription avec le site de liaison des facteurs de transcription Ets créé par ce polymorphisme nucléotidique simple ou résultant de celui-ci, ainsi que des méthodes d'utilisation de ces agents pour le traitement des maladies associées à la métalloprotéinase matricielle 1.
PCT/US1999/026610 1998-11-30 1999-11-10 Methodes de diagnostic, de pronostic et de traitement des maladies associees a la metalloproteinase matricielle 1 via un polymorphisme nucleotidique simple de cette metalloproteinase matricielle 1 Ceased WO2000032819A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US09/856,749 US7033756B1 (en) 1998-11-30 1999-11-10 Methods of diagnosing, prognosticating and treating matrix metalloproteinase-1 related diseases via a matrix metalloproteinase-1 single nucleotide polymorphism
US11/408,202 US7473774B2 (en) 1998-11-30 2006-04-20 Kit for diagnosing and prognosticating matrix metalloproteinase-1 related disease via a matrix metalloproteinase-1 single nucleotide polymorphism

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11026698P 1998-11-30 1998-11-30
US60/110,266 1998-11-30

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09856749 A-371-Of-International 1999-11-10
US11/408,202 Continuation US7473774B2 (en) 1998-11-30 2006-04-20 Kit for diagnosing and prognosticating matrix metalloproteinase-1 related disease via a matrix metalloproteinase-1 single nucleotide polymorphism

Publications (1)

Publication Number Publication Date
WO2000032819A1 true WO2000032819A1 (fr) 2000-06-08

Family

ID=22332086

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/026610 Ceased WO2000032819A1 (fr) 1998-11-30 1999-11-10 Methodes de diagnostic, de pronostic et de traitement des maladies associees a la metalloproteinase matricielle 1 via un polymorphisme nucleotidique simple de cette metalloproteinase matricielle 1

Country Status (1)

Country Link
WO (1) WO2000032819A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003025198A3 (fr) * 2001-09-17 2004-01-08 Internat Genomics Llc Polymorphismes regulateurs d'un nucleotide simple et procedes associes
WO2005027830A3 (fr) * 2003-09-12 2005-09-22 Univ Virginia Commonwealth Oligonucleotides chimeres, leurres des facteurs de transcription

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5744442A (en) * 1992-08-26 1998-04-28 Bristol Meyers Squibb Company Regulation of cellular invasiveness

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5744442A (en) * 1992-08-26 1998-04-28 Bristol Meyers Squibb Company Regulation of cellular invasiveness

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
LOGAN ET AL.: "Synergistic Transcriptional Activation of the Tissue Inhibitor of Metalloproteinase-1 Promoter via Functional Interaction of AP-1 and Ets-1 Transcription Factors", vol. 271, no. 2, 12 January 1996 (1996-01-12), pages 774 - 782, XP002923237 *
RUTTER ET AL.: "A Single Nucleotide Polymorphism in the Matrix Metalloproteinase-1 Promoter Creates and Ets Binding and Augments Transcription", CANCER RESEARCH,, vol. 58, 1 December 1998 (1998-12-01), pages 5321 - 5325, XP002923238 *
WESTERMARCK ET AL.: "Differential regulation of interstitial collagenase (NMP-1) gene expression by ETS transcription factors", ONCOGENE,, vol. 14, 1997, pages 2651 - 2660, XP002923239 *
WHITE ET AL.: "ETS Sites in the promoters of the Matrix Metalloproteinases Collagenase (NMP-1) Stromelysin (MMP-3) are Auxiliary Elements that Regulate Basal an Phorbol-Induced Transcription", CONNECTIVE TISSUE RESEARCH,, vol. 36, no. 4, 1997, pages 321 - 335, XP002923240 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003025198A3 (fr) * 2001-09-17 2004-01-08 Internat Genomics Llc Polymorphismes regulateurs d'un nucleotide simple et procedes associes
WO2005027830A3 (fr) * 2003-09-12 2005-09-22 Univ Virginia Commonwealth Oligonucleotides chimeres, leurres des facteurs de transcription

Similar Documents

Publication Publication Date Title
Rutter et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription
Hui et al. Loss of heterozygosity on the long arm of chromosome 11 in nasopharyngeal carcinoma
Belaaouaj et al. Human macrophage metalloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression
Price et al. Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation
US8071304B2 (en) Methods for detecting a polymorphism in the NFKB1 gene promoter
Davies et al. Sequence variations in the first exon of alpha-galactosidase A.
CA2327538A1 (fr) Polymorphismes du gene de mmp-9
US9556488B2 (en) Spinocerebellar ataxia type 8 and methods of detection
CA2330206A1 (fr) Genes de poly(adp-ribose)polymerase
WO2000079003A1 (fr) Polymorphismes du gene de hmg-coa reductase humaine
KR20010092687A (ko) ＭｘＡ단백질의 다형 유전자 및 그 사용방법
US7473774B2 (en) Kit for diagnosing and prognosticating matrix metalloproteinase-1 related disease via a matrix metalloproteinase-1 single nucleotide polymorphism
WO2000032819A1 (fr) Methodes de diagnostic, de pronostic et de traitement des maladies associees a la metalloproteinase matricielle 1 via un polymorphisme nucleotidique simple de cette metalloproteinase matricielle 1
Brinckmann et al. Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point mutation (W612C)
Erdmann et al. Screening the human bradykinin B2 receptor gene in patients with cardiovascular diseases: identification of a functional mutation in the promoter and a new coding variant (T21M)
WO2008087049A1 (fr) Marqueur de diagnostic et plate-forme de conception de médicament dans les cas d'infarctus du myocarde et d'insuffisance cardiaque
Dybkær et al. Single site polymorphisms and alternative splicing of the human CD13 gene–different splicing frequencies among patients with acute myeloid leukaemia and healthy individuals
JP2017135985A (ja) Ｂ前駆細胞性急性リンパ芽球性白血病新規キメラ遺伝子
Ito et al. Gene structure and chromosome mapping of mouse transcription elongation factor S-II (Tcea1)
EP1100961A1 (fr) Polymorphismes genetiques dans le gene du recepteur humain des neurokinines 2 et leur utilisation dans le diagnostic et traitement de maladies
US20100196957A1 (en) Cloning and characterization of 5' flanking regions of a human aggrecanase-1 gene
WO2002046462A2 (fr) Variants genetiques fonctionels
Rutter Cell-type specific expression of matrix metalloproteinase-1 (MMP-1)
US20070299024A1 (en) Cloning And Characterization Of 5'Flanking Regions Of A Human Aggrecanase-1 Gene
JP2000175689A (ja) ヒトミトコンドリアｄｎａ異常の検出方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
WWE Wipo information: entry into national phase

Ref document number: 09856749

Country of ref document: US