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Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2003

01.06.2003 | Original Paper

Analysis of DLC-1 expression in human breast cancer

verfasst von: Marlies Plaumann, Susanne Seitz, Renate Frege, Lope Estevez-Schwarz, Siegfried Scherneck

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2003

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Abstract

The chromosome region 8p12-p22 shows frequent allelic loss in many neoplasms, including breast cancer (BC). The DLC-1 gene, located on 8p21-p22, might be a candidate tumor suppressor gene in this region. To evaluate the involvement of DLC-1 in breast carcinogenesis we studied DLC-1 mRNA expression in a panel of 14 primary human BC and the corresponding normal breast cells as well as 8 BC cell lines. Low levels or absence of DLC-1 mRNA were observed in 57% of primary BC and 62.5% of BC cell lines, respectively. We could not find any correlation between DLC-1mRNA expression and deletions at the DLC-1 locus. Transfection of the gene into DLC-1 deficient T-47D cells raised the DLC-1 mRNA level and resulted in inhibition of cell growth and reduced colony-forming capacity. Our results indicate a role of DLC-1 in BC carcinogenesis.
Literatur
Zurück zum Zitat Adélaide J, Chaffanet M, Imbert A, Allione F, Geneix J, Popovici C, van Alewijk D, Trapman J, Zeillinger R, Borresen-Dale AL, Lidereau R, Birnbaum D, Pebusque MJ (1998) Chromosome region 8p11-p21: refined mapping and molecular alterations in breast cancer. Genes Chromosomes Cancer 22:186–199CrossRefPubMed Adélaide J, Chaffanet M, Imbert A, Allione F, Geneix J, Popovici C, van Alewijk D, Trapman J, Zeillinger R, Borresen-Dale AL, Lidereau R, Birnbaum D, Pebusque MJ (1998) Chromosome region 8p11-p21: refined mapping and molecular alterations in breast cancer. Genes Chromosomes Cancer 22:186–199CrossRefPubMed
Zurück zum Zitat Ambashagan R, Fujii H, Gabrielson E (1998) Allelic loss of chromosomal arm 8p in breast cancer progression. Am J Pathol 152:815–819PubMed Ambashagan R, Fujii H, Gabrielson E (1998) Allelic loss of chromosomal arm 8p in breast cancer progression. Am J Pathol 152:815–819PubMed
Zurück zum Zitat Choi C, Kim MH, Juhng SW, Oh BR (2000) Loss of heterozygosity at chromosome segments 8p22 and 8p11.2–21.1 in transitional-cell carcinoma of the urinary bladder. Int J Cancer 86:501–505CrossRefPubMed Choi C, Kim MH, Juhng SW, Oh BR (2000) Loss of heterozygosity at chromosome segments 8p22 and 8p11.2–21.1 in transitional-cell carcinoma of the urinary bladder. Int J Cancer 86:501–505CrossRefPubMed
Zurück zum Zitat El-Naggar AK, Coombes MM, Batsakis JG, Hong WK, Goepfert H, Kagan J (1998) Localization of chromosome 8p regions in valued in early tumorigenesis of oral and laryngeal squamous carcinoma. Onocgene 16:2983–2987CrossRef El-Naggar AK, Coombes MM, Batsakis JG, Hong WK, Goepfert H, Kagan J (1998) Localization of chromosome 8p regions in valued in early tumorigenesis of oral and laryngeal squamous carcinoma. Onocgene 16:2983–2987CrossRef
Zurück zum Zitat Farrington SM, Cunningham C, Boyle SM, Wyllie Ah, Dunlop MG (1996) Detailed physical and deletion mapping of 8p with isolation of YAC clones from tumour suppressor loci involved in colorectal cancer. Oncogene 12:1803–1808PubMed Farrington SM, Cunningham C, Boyle SM, Wyllie Ah, Dunlop MG (1996) Detailed physical and deletion mapping of 8p with isolation of YAC clones from tumour suppressor loci involved in colorectal cancer. Oncogene 12:1803–1808PubMed
Zurück zum Zitat Goldberg EK, Glendening M, Karanjawala Z, Sridhar A, Walker GJ, Hayward NK, Rice AJ, Kurera D, Tebha Y, Fountain JW (2000) Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletion analysis. Am J Hum Genet 67:417–431CrossRefPubMed Goldberg EK, Glendening M, Karanjawala Z, Sridhar A, Walker GJ, Hayward NK, Rice AJ, Kurera D, Tebha Y, Fountain JW (2000) Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletion analysis. Am J Hum Genet 67:417–431CrossRefPubMed
Zurück zum Zitat Hamaguchi M, Meth JL, von Clitzing C, Wei W, Esposito D, Rodgers L, Walsh T, Welcsh P, King M-C, Wigle MH (2002) DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 99:1347–13652CrossRefPubMed Hamaguchi M, Meth JL, von Clitzing C, Wei W, Esposito D, Rodgers L, Walsh T, Welcsh P, King M-C, Wigle MH (2002) DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 99:1347–13652CrossRefPubMed
Zurück zum Zitat Ishii H, Vecchione A, Murakumo Y, Baldassarre G, Numata S, Trapasso F, Alder H, Baffa R, Croce CM (2001) FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc Natl Acad Sci USA 98:10374–10379CrossRefPubMed Ishii H, Vecchione A, Murakumo Y, Baldassarre G, Numata S, Trapasso F, Alder H, Baffa R, Croce CM (2001) FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc Natl Acad Sci USA 98:10374–10379CrossRefPubMed
Zurück zum Zitat Kerangueven F, Essioux L, Dib A, Noguchi T, Allione F, Geneix J, Longy M, Lidereau R, Eisinger F, Pebusque MJ, Jacquemier J, Bonaiti-Pellie C, Sobol H, Birnbaum D (1995) Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8. Oncogene 10:1023–1026PubMed Kerangueven F, Essioux L, Dib A, Noguchi T, Allione F, Geneix J, Longy M, Lidereau R, Eisinger F, Pebusque MJ, Jacquemier J, Bonaiti-Pellie C, Sobol H, Birnbaum D (1995) Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8. Oncogene 10:1023–1026PubMed
Zurück zum Zitat Ng IO, Liang ZD, Cao L, Lee TK (2000) DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer Res 60:6581–6584PubMed Ng IO, Liang ZD, Cao L, Lee TK (2000) DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer Res 60:6581–6584PubMed
Zurück zum Zitat Peck J, Douglasiv G, Wu CH, Burbelo PD (2000) Human RhoGAP domain-containing proteins: Structure, function and evolutionary relationship. FEBS Lett 528:27–34CrossRef Peck J, Douglasiv G, Wu CH, Burbelo PD (2000) Human RhoGAP domain-containing proteins: Structure, function and evolutionary relationship. FEBS Lett 528:27–34CrossRef
Zurück zum Zitat Pineau P, Nagai H, Prigent S, Wei Y, Gyapay G, Weissenbach J, Tiollais P, Buendia MA, Dejean A (1999) I dentification of three distinct regions of allelic deletions on the short arm of chromosome 8 in hepatocellular carcinoma. Oncogene 18:3127–3134PubMed Pineau P, Nagai H, Prigent S, Wei Y, Gyapay G, Weissenbach J, Tiollais P, Buendia MA, Dejean A (1999) I dentification of three distinct regions of allelic deletions on the short arm of chromosome 8 in hepatocellular carcinoma. Oncogene 18:3127–3134PubMed
Zurück zum Zitat Pribill I, Speiser P, Leary J, Leodolter S, Hacker NF, Friedlander ML, Birnbaum D, Zeillinger R, Krainer M (2001) High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma. Cytogenet Cell Genet 129:23–29CrossRef Pribill I, Speiser P, Leary J, Leodolter S, Hacker NF, Friedlander ML, Birnbaum D, Zeillinger R, Krainer M (2001) High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma. Cytogenet Cell Genet 129:23–29CrossRef
Zurück zum Zitat Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB (1999) Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Nat Cancer Inst 91:1574–1580CrossRef Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB (1999) Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Nat Cancer Inst 91:1574–1580CrossRef
Zurück zum Zitat Schmitz AAP, Govek EE, Böttner B, van Aelst L (2000) Rho GTPases: Signaling, migration, and invasion. Exp Cell Res 261:1–12PubMed Schmitz AAP, Govek EE, Böttner B, van Aelst L (2000) Rho GTPases: Signaling, migration, and invasion. Exp Cell Res 261:1–12PubMed
Zurück zum Zitat Seitz S, Rohde K, Bender E, Nothnagel A, Pidde H, Ullrich OM, El-Zeheiry A, Haensch W, Jandrig B, Kölble K, Schlag PM, Scherneck S (1997a) Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis. Br J Cancer 76:983–991PubMed Seitz S, Rohde K, Bender E, Nothnagel A, Pidde H, Ullrich OM, El-Zeheiry A, Haensch W, Jandrig B, Kölble K, Schlag PM, Scherneck S (1997a) Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis. Br J Cancer 76:983–991PubMed
Zurück zum Zitat Seitz S, Rohde K, Bender E, Nothnagel A, Kölble K, Schlag PM, Scherneck S (1997b) Strong indication for a breast cancer susceptibility gene on chromosome 8p12-p22: linkage analysis in German breast cancer families. Oncogene 14:741–743 Seitz S, Rohde K, Bender E, Nothnagel A, Kölble K, Schlag PM, Scherneck S (1997b) Strong indication for a breast cancer susceptibility gene on chromosome 8p12-p22: linkage analysis in German breast cancer families. Oncogene 14:741–743
Zurück zum Zitat Seitz S, Werner S, Fischer J, Nothnagel A, Schlag PM, Scherneck S (2000) Refined deletion mapping in sporadic breast cancer at chromosomal region 8p12-p21 and association with clinicopathological parameters. Eur J Cancer 36:1507–1513CrossRefPubMed Seitz S, Werner S, Fischer J, Nothnagel A, Schlag PM, Scherneck S (2000) Refined deletion mapping in sporadic breast cancer at chromosomal region 8p12-p21 and association with clinicopathological parameters. Eur J Cancer 36:1507–1513CrossRefPubMed
Zurück zum Zitat Seitz S, Wassmuth P, Fischer J, Nothnagel A, Jandrig B, Schlag PM, Scherneck S (2002) Mutation analysis and mRNA expression of TRAIL-receptors in human breast cancer. Int J Cancer 102:117–128CrossRefPubMed Seitz S, Wassmuth P, Fischer J, Nothnagel A, Jandrig B, Schlag PM, Scherneck S (2002) Mutation analysis and mRNA expression of TRAIL-receptors in human breast cancer. Int J Cancer 102:117–128CrossRefPubMed
Zurück zum Zitat Ugolini F, Adélaide J, Charafe-Jauffret E, Nguyen C, Jacquemir J, Jordan B, Birnbaum D, Pebusque M-J (1999) Differential expression assay of chromosome arm 8p genes identifies frizzle-related (FRP1/FRZB) and fibroblast growth factor receptor 1 (FGFR1) as candidate breast cancer genes. Oncogene 18:1903–1910CrossRefPubMed Ugolini F, Adélaide J, Charafe-Jauffret E, Nguyen C, Jacquemir J, Jordan B, Birnbaum D, Pebusque M-J (1999) Differential expression assay of chromosome arm 8p genes identifies frizzle-related (FRP1/FRZB) and fibroblast growth factor receptor 1 (FGFR1) as candidate breast cancer genes. Oncogene 18:1903–1910CrossRefPubMed
Zurück zum Zitat Washburn JG, Wojno KJ, Dey J, Powell IJ, Macoska JA (2000) 8pter-p23 deletion is associated with racial differences in prostate cancer outcome. Clin Cancer Res 6:4647–4652PubMed Washburn JG, Wojno KJ, Dey J, Powell IJ, Macoska JA (2000) 8pter-p23 deletion is associated with racial differences in prostate cancer outcome. Clin Cancer Res 6:4647–4652PubMed
Zurück zum Zitat Wilson PJ, McGlinn E, Marsh A, Evans T, Arnold J, Wright K, Biden K, Young J, Weinwright B, Wicking C, Chenevix-Tranch, G (2000) Sequence variants of DLC-1 in colorectal and ovarian tumours. Hum Mutat 15:156–165CrossRefPubMed Wilson PJ, McGlinn E, Marsh A, Evans T, Arnold J, Wright K, Biden K, Young J, Weinwright B, Wicking C, Chenevix-Tranch, G (2000) Sequence variants of DLC-1 in colorectal and ovarian tumours. Hum Mutat 15:156–165CrossRefPubMed
Zurück zum Zitat Wistuba II, Behrens C, Virmani AK, Milchgrub S, Syed S, Lam S, Mackay B, Minna JD, Gazdar AF (1999) Allelic losses at chromosome 8p21–23 are early and frequent events in the pathogenesis of lung cancer. Cancer Res 59:1973–1979PubMed Wistuba II, Behrens C, Virmani AK, Milchgrub S, Syed S, Lam S, Mackay B, Minna JD, Gazdar AF (1999) Allelic losses at chromosome 8p21–23 are early and frequent events in the pathogenesis of lung cancer. Cancer Res 59:1973–1979PubMed
Zurück zum Zitat Yin XL, Pang JC, Ng HK (2000) Identification of a region of homozygous deletion on 8p22–23.1 in medulloblastoma. Oncogene 21:1461–1468CrossRef Yin XL, Pang JC, Ng HK (2000) Identification of a region of homozygous deletion on 8p22–23.1 in medulloblastoma. Oncogene 21:1461–1468CrossRef
Zurück zum Zitat Yokota T. Yoshimoto M, Akiyama F, Sakameto G, Kasumi F, Nakamura Y, Emi M (1999) Localization of a tumor suppressor gene associated with the progression of human breast carcinoma within a 1-cM interval of 8p22-p23.1. Cancer 85:447–452CrossRefPubMed Yokota T. Yoshimoto M, Akiyama F, Sakameto G, Kasumi F, Nakamura Y, Emi M (1999) Localization of a tumor suppressor gene associated with the progression of human breast carcinoma within a 1-cM interval of 8p22-p23.1. Cancer 85:447–452CrossRefPubMed
Zurück zum Zitat Yuan B-Z, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC (1998) Cloning, characterization and chromosomal localization of a gene frequently deleted in human liver Cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 58:2196–2199PubMed Yuan B-Z, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC (1998) Cloning, characterization and chromosomal localization of a gene frequently deleted in human liver Cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 58:2196–2199PubMed
Zurück zum Zitat Yuan B-Z, Thorgeirsson SS, Eyfjord J, Gudmundsdottir K, Popescu NC (2000) Genomic deletion and DNA hypermethylation of DLC-1, a candidate tumor suppressor gene in several human solid tumors. Proc Am Assoc Cancer Res 41:105 Yuan B-Z, Thorgeirsson SS, Eyfjord J, Gudmundsdottir K, Popescu NC (2000) Genomic deletion and DNA hypermethylation of DLC-1, a candidate tumor suppressor gene in several human solid tumors. Proc Am Assoc Cancer Res 41:105
Metadaten
Titel
Analysis of DLC-1 expression in human breast cancer
verfasst von
Marlies Plaumann
Susanne Seitz
Renate Frege
Lope Estevez-Schwarz
Siegfried Scherneck
Publikationsdatum
01.06.2003
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2003
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-003-0440-z

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