Skip to main content
SpringerLink
Log in

The minimal Tumor Suppressor in Lung Cancer-1 promoter is restrained by an inhibitory region

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Tumor Suppressor in Lung Cancer-1 (TSLC1) expression is repressed in many different cancers. Hypermethylation of six CpG sites upstream of the TSLC1 coding region is correlated with TSLC1 repression. However, the functional elements of the TSLC1 promoter have not been examined. In this study, the transcription start site was identified as being 67 or 62 bp upstream of the translational start site by primer extension and bioinformatics analysis of expressed sequence tags (ESTs), respectively. Two promoter regions that regulate TSLC1 expression were identified. One, a small region of 170 bp, including 107 bp upstream of the transcription initiation site, is sufficient to generate maximal TSLC1 promoter activity. This minimal promoter does not contain the CpG sites that are hypermethylated in repressed TSLC1 promoters. Two, the maximal activity of the TSLC1 promoter is dampened by an inhibitory region that resides upstream of the minimal promoter.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Murakami Y (2005) Involvement of a cell adhesion molecule, TSLC1/IGSF4, in human oncogenesis. Cancer Sci 96(9):543–552. doi:10.1111/j.1349-7006.2005.00089.x

    Article  CAS  PubMed  Google Scholar 

  2. Yamada D et al (2006) Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule. Mol Cell Biol 26(9):3610–3624. doi:10.1128/MCB.26.9.3610-3624.2006

    Article  CAS  PubMed  Google Scholar 

  3. van der Weyden L et al (2006) Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of spermatogenesis. Mol Cell Biol 26(9):3595–3609. doi:10.1128/MCB.26.9.3595-3609.2006

    Article  PubMed  CAS  Google Scholar 

  4. Kuramochi M et al (2001) TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet 27(4):427–430. doi:10.1038/86934

    Article  CAS  PubMed  Google Scholar 

  5. Ito A et al (2008) Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium. Lab Invest 88(5):504–514. doi:10.1038/labinvest.2008.15

    Article  CAS  PubMed  Google Scholar 

  6. Koma Y et al (2008) Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions. Gastroenterology 134(5):1544–1554. doi:10.1053/j.gastro.2008.01.081

    Article  CAS  PubMed  Google Scholar 

  7. Gomyo H et al (1999) A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2. Genomics 62(2):139–146. doi:10.1006/geno.1999.6001

    Article  CAS  PubMed  Google Scholar 

  8. Fujita E, Soyama A, Momoi T (2003) RA175, which is the mouse ortholog of TSLC1, a tumor suppressor gene in human lung cancer, is a cell adhesion molecule. Exp Cell Res 287(1):57–66. doi:10.1016/S0014-4827(03)00095-8

    Article  CAS  PubMed  Google Scholar 

  9. Watabe K et al (2003) IGSF4: a new intercellular adhesion molecule that is called by three names, TSLC1, SgIGSF and SynCAM, by virtue of its diverse function. Histol Histopathol 18(4):1321–1329

    CAS  PubMed  Google Scholar 

  10. Shingai T et al (2003) Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell–cell adhesion and transmembrane protein localization in epithelial cells. J Biol Chem 278(37):35421–35427. doi:10.1074/jbc.M305387200

    Article  CAS  PubMed  Google Scholar 

  11. Uchino K et al (2003) Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung. Cancer 98(5):1002–1007. doi:10.1002/cncr.11599

    Article  CAS  PubMed  Google Scholar 

  12. Lung HL et al (2004) Fine mapping of the 11q22–23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer 112(4):628–635. doi:10.1002/ijc.20454

    Article  CAS  PubMed  Google Scholar 

  13. Steenbergen RD et al (2004) TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst 96(4):294–305

    Article  CAS  PubMed  Google Scholar 

  14. Surace EI et al (2004) Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival. J Neuropathol Exp Neurol 63(10):1015–1027

    CAS  PubMed  Google Scholar 

  15. Sasaki H et al (2005) Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia. Blood 105(3):1204–1213. doi:10.1182/blood-2004-03-1222

    Article  CAS  PubMed  Google Scholar 

  16. Kitamura Y et al (2009) Frequent overexpression of CADM1/IGSF4 in lung adenocarcinoma. Biochem Biophys Res Commun 383(4):480–484. doi:10.1016/j.bbrc.2009.04.039

    Article  CAS  PubMed  Google Scholar 

  17. Fukami T et al (2003) Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines. Int J Cancer 107(1):53–59. doi:10.1002/ijc.11348

    Article  CAS  PubMed  Google Scholar 

  18. Tamura G (2004) Promoter methylation status of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia. Histol Histopathol 19(1):221–228

    CAS  PubMed  Google Scholar 

  19. Lindsey JC et al (2004) Identification of tumour-specific epigenetic events in medulloblastoma development by hypermethylation profiling. Carcinogenesis 25(5):661–668. doi:10.1093/carcin/bgh055

    Article  CAS  PubMed  Google Scholar 

  20. Hui AB et al (2003) Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 38(4):170–178. doi:10.1002/mc.10156

    Article  CAS  PubMed  Google Scholar 

  21. Honda T et al (2002) Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res 93(8):857–860

    CAS  PubMed  Google Scholar 

  22. Jansen M et al (2002) Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs. Cancer Biol Ther 1(3):293–296

    CAS  PubMed  Google Scholar 

  23. Fukuhara H et al (2002) Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer. Jpn J Cancer Res 93(6):605–609

    CAS  PubMed  Google Scholar 

  24. Carey M, Smale S (2000) Transcriptional regulation in eukaryotes: concepts, strategies, techniques. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  25. Sambrook J, Fritsch EF, Maniatis T (eds) (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Planview

    Google Scholar 

  26. Lo K, Smale ST (1996) Generality of a functional initiator consensus sequence. Gene 182(1–2):13–22. doi:10.1016/S0378-1119(96)00438-6

    Article  CAS  PubMed  Google Scholar 

  27. Crosby ME, Almasan A (2004) Opposing roles of E2Fs in cell proliferation and death. Cancer Biol Ther 3(12):1208–1211. doi:10.4161/cbt.3.12.1494

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been supported by a grant from Department of Energy/University of Tennessee Cancer Institute to RH.

Author information

Authors and Affiliations

  1. Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN, 38163, USA

    Roderick T. Hori

Authors
  1. Roderick T. Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roderick T. Hori.

Electronic supplementary material

Below is the link to the electronic supplementary material.

(PDF 149 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hori, R.T. The minimal Tumor Suppressor in Lung Cancer-1 promoter is restrained by an inhibitory region. Mol Biol Rep 37, 1979–1985 (2010). https://doi.org/10.1007/s11033-009-9646-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9646-8

Keywords

Search

Navigation