Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

Oncogene volume 22, pages 445–450 (2003)Cite this article

Abstract

The human DLC-1 (deleted in liver cancer 1) gene was cloned from a primary human hepatocellular carcinoma (HCC) and mapped to the chromosome 8p21–22 region frequently deleted in common human cancers and suspected to harbor tumor suppressor genes. DLC-1 was found to be deleted or downregulated in a significant number of HCCs. We expanded our investigations to other cancers with recurrent deletions of 8p22, and in this study examined alterations of DLC-1 in primary human breast tumors, human breast, colon, and prostate tumor cell lines. Genomic deletion of DLC-1 was observed in 40% of primary breast tumors, whereas reduced or undetectable levels of DLC-1 mRNA were seen in 70% of breast, 70% of colon, and 50% of prostate tumor cell lines To see whether DLC-1 expression affects cell growth and tumorigenicity, two breast carcinoma cell lines lacking the expression of endogenous gene were transfected with the DLC-1 cDNA. In both cell lines, DLC-1 transfection caused significant growth inhibition and reduction of colony formation. Furthermore, introduction of the DLC-1 cDNA abolished the in vivo tumorigenicity in nude mice, suggesting that the DLC-1 gene plays a role in breast cancer by acting as a bona fide tumor suppressor gene.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Arbieva ZH, Banerjee K, Kim SY, Edassery SL, Maniatis VS, Horrigan SK and Westbrook CA . (2000). Genome Res., 10, 244–257.

  • Boetter B and van Aelst L . (2002). Gene, 286, 155–174.

  • Borkhardt A, Bojesen S, Haas OA, Fuchs U, Bartelheimer D, Loncarevic IF, Bohle RM, Harbott J, Repp R, Jaeger U, Viehmann S, Henn T, Korth P, Scharr D and Lampert F . (2000). Proc. Natl. Acad. Sci. USA, 97, 9168–9173.

  • Cabeza-Arvelaiz Y, Sepulveda JL, Lebovitz RM, Thompson TC and Chinault AC . (2001). Oncogene, 31, 4169–4179.

  • Durkin ME, Yuan B-Z, Thorgeirsson SS and Popescu NC . (2002), Gene, 288, 119–127.

  • Euer N, Schwirzke M, Evtimova V, Burtscher H, Jarsch M, Tarin D and Weidle U . (2002), Anticancer Res., 22, 733–740.

  • Gustafson CE, Wilson PJ, Lukeis R, Baker E, Woolatt E, Annab L, Hawke L, Barrett J and Chenevix-Trench G . (1996).Cancer Res., 56, 5238–5245.

  • Homma Y and Emori Y . (1995). EMBO J., 14, 286–291.

  • Jaffe AB and Hall A . (2002). Adv. Cancer Res., 84, 57–80.

  • Jenkins R, Takahashi S, DeLacey K, Bergstralh E and Lieber M . (1998). Genes Chromosomes Cancer, 21, 131–143.

  • Martinez-Climent JA, Vizcarra E, Sanchez D, Blesa D, Marugan I, Benet I, Sole F, Rubio-Moscardo F, Terol MJ, Climent J, Sarsotti E, Tormo M, Andreu E, Sallido M, Ruiz MA, Prosper F, Siebert R, Dyer MJS and Garcia-Conde J . (2001). Blood, 98, 3479–3482.

  • Nagase T, Seki N, Ishikawa K, Tanaka and Nomura N . (1996). DNA Res., 3, 17–24.

  • Ng IO, Liang Z-D, Cao L and Lee TK . (2000), Cancer Res., 60, 6581–6581.

  • Ponting CP and Aravind L . (1999). Trends Biochem. Sci., 24, 130–132.

  • Qin LX, Tang ZY, Sham JS, Ma ZC, Ye SL, Zhou XD, Wu ZQ, Trent JM and Guan XY . (1999). Cancer Res., 59, 5662–5665.

  • Qin LX, Tang ZY, Ye SL, Liu YK, Ma ZC, Zhou XD, Wu ZQ, Lin ZY, Sun FX, Tian J, Guan XY, Pack SD and Zhuang ZP . (2001). J. Cancer Res. Clin. Oncol., 127, 482–488.

  • Sekimata M, Kabuyama Y, Emori Y and Homma Y . (1999). Biol. Chem., 274, 17757–17762.

  • Tikoo A, Czekay S, Viars C, White S, Heath JK, Arden K and Maruta H . (2000). Gene 257, 23–31.

  • Tirkkonen MTM, Karhu R, Kallioniemi A, Isola J and Kallioniemi OP . (1998). Genes Chromosomes Cancer, 21, 177–184.

  • Wilson PJ, McGlinn E, Marsh A, Evans T, Arnold J, Wright K, Biden K, Young J, Wainwright B, Wicking C and ChenevixTrench G . (2000). Human Mut., 15, 156–165.

  • Xu J, Zheng SL, Hawkins GA, Faith DA, Kelly B, Isaacs SD, Wiley KE, Chang B, Ewing CM, Bujnovszky P, Carpten JD, Bleecker ER, Walsh PC, Trent JM, Meyers DA and Isaacs WB . (2001). Am. J. Hum. Genet., 69, 341–350.

  • Yaremko ML, Kutza C, Lyzak J, Mick R, Recant WM and Westbrook CA . (1998). Genes Chromosomes Cancer, 21, 189–195.

  • Yoshioka K, Matsumara F, Akedo H and Itoh K . (1998). J. Biol. Chem., 273, 5146–5154.

  • Yuan BZ, Durkin ME and Popescu NC . (2002). Cancer Genet. Cytogenet., in press.

  • Yuan B-Z, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS and Popescu NC . (1998). Cancer Res., 58, 2196–2199.

  • Yuan B-Z, Thorgeirsson SS, Eyfjord J, Gudmundsdottir K and Popescu NC . (2000). Proc. Am. Assoc. Cancer Res, 41, 105.

  • Yuan BZ, Yang Y, Keck–Waggoner CL, Zimonjic DB, Thorgeirsson SS and Popescu NC . (1999). Cytogenet. Cell Genet., 87, 189–190.

  • Zimonjic DB, Keck-Waggoner CL, Yuan B-Z, Kraus MH and Popescu NC . (2000). Int. J. Oncol., 16, 221–230.

  • Zitzelsberger H, Lehmann L, Werner M and Bauchinger M . (1997). Histochem. Cell. Biol., 108, 403–417.

Download references

Author information

Author notes

  1. Bao-Zhu Yuan

    Present address: Toxicology and Molecular Biology Branch, Health Effects, Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA

  2. Bao-Zhu Yuan and Xiaoling Zhou: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, 20892, MD, USA

    Bao-Zhu Yuan, Xiaoling Zhou, Marian E Durkin, Drazen B Zimonjic, Snorri S Thorgeirsson & Nicholas C Popescu

  2. Icelandic Cancer Society, Reykjavik, Iceland

    Katrin Gumundsdottir & Jorunn E Eyfjord

Authors
  1. Bao-Zhu Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoling Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marian E Durkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Drazen B Zimonjic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katrin Gumundsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jorunn E Eyfjord
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Snorri S Thorgeirsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicholas C Popescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicholas C Popescu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuan, BZ., Zhou, X., Durkin, M. et al. DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity. Oncogene 22, 445–450 (2003). https://doi.org/10.1038/sj.onc.1206064

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206064

Keywords

This article is cited by

Search

Advanced search

Quick links