Skip to main content
Log in

Increased expression of hLRH-1 in human gastric cancer and its implication in tumorigenesis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Altered signaling pathways or deregulated transcription factors represent an important category of molecular events leading to aberrant gene regulation in gastric cancer, among which the role of WNT/β-catenin pathway remains unclear. LRH-1 is a critical transcription factor in controlling cell proliferation via crosstalk with the β-catenin signaling pathway. In order to gain a knowledge of the expression of hLRH-1v1 and hLRH-1 in gastric cancer, a Q-PCR analysis was carried out. Our results showed that in about 50 and 47.6% of 42 tested patients with gastric cancer, the mRNA expression of hLRH-1v1 and hLRH-1 was significantly upregulated, as compared with self-paired normal control, respectively. Besides, overexpression of hLRH-1 was shown to promote the proliferation of gastric adenocarcinoma cell SGC-7901 via induction of cyclin E1. Taken together, our present study demonstrated for the first time the increased expression of hLRH-1v1 and hLRH-1 in human gastric cancer, an alteration which may implicate in tumorigenesis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

LRH-1:

Liver receptor homolog 1

RT:

Reverse transcription

Q-PCR:

Real-time quantitative polymerase chain reaction

References

  1. Wu M, Xue K (2004) Genetics of tumor. Scientific Press, Beijing, pp 409–435

    Google Scholar 

  2. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 1000:57–70

    Article  Google Scholar 

  3. Stock M, Otto F (2005) Gene deregulation in gastric cancer. Gene 360:1–19

    Article  PubMed  CAS  Google Scholar 

  4. Fayard E, Auwerx J, Schoonjans K (2004) LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol 14:250–260

    Article  PubMed  CAS  Google Scholar 

  5. Luo Y, Liang CP, Tall AR (2001) The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J Biol Chem 276:24767–24773

    Article  PubMed  CAS  Google Scholar 

  6. Schoonjans K, Annicotte J, Huby T et al (2002) Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I. EMBO R 3:1181–1187

    Article  CAS  Google Scholar 

  7. Goodwin B, Jones SA, Price RR et al (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 6:517–526

    Article  PubMed  CAS  Google Scholar 

  8. Lu TT, Makishima M, Repa JJ et al (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6:507–515

    Article  PubMed  CAS  Google Scholar 

  9. Botrugno OA, Fayard E, Annicotte J et al (2004) Synergy between LRH-1 and β-catenin induces G1 cyclin-mediated cell proliferation. Mol Cell 15:499–509

    Article  PubMed  CAS  Google Scholar 

  10. Zhou J, Suzuki T, Kovacic A et al (2005) Interactions between prostaglandin E2, liver receptor homologue-1, and aromatase in breast cancer. Cancer Res 65:657–663

    PubMed  CAS  Google Scholar 

  11. Annicotte JS, Chavey C, Servant N et al (2005) The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene. Oncogene 24:8167–8175

    PubMed  CAS  Google Scholar 

  12. Schoonjans K, Dubuquoy L, Mebis J, et al (2005) Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation. Proc Natl Acad Sci USA 102:2058–2062

    Article  PubMed  CAS  Google Scholar 

  13. Nitta M, Ku S, Brown C et al (1999) CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7α-hydroxylase gene. Proc Natl Acad Sci USA 96:6660–6665

    Article  PubMed  CAS  Google Scholar 

  14. Candidus S, Bischoff P, Becker KF et al (1996) No evidence for mutations in the alpha- and beta-catenin genes in human gastric and breast carcinomas. Cancer Res 56:49–52

    PubMed  CAS  Google Scholar 

  15. Woo DK, Kim HS, Lee HS et al (2001) Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines. Int J Cancer 95:108–113

    Article  PubMed  CAS  Google Scholar 

  16. Lee JH, Abraham SC, Kim HS et al (2002) Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma. Am J Pathol 161:611–618

    PubMed  CAS  Google Scholar 

  17. Abraham SC, Park SJ, Lee JH et al (2003) Genetic alterations in gastric adenomas of intestinal and foveolar phenotypes. Mod Path 16:786–795

    Article  Google Scholar 

  18. Moon RT, Kohn AD, De Ferrari GV et al (2004) WNT and β-catenin signalling: diseases and therapies. Nat Rev 5:689–699

    Google Scholar 

  19. Morin PJ, Sparks AB, Korinek V et al (1997) Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science 275:1787–1790

    Article  PubMed  CAS  Google Scholar 

  20. Tetsu O, McCormick F (1999) β-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426

    Article  PubMed  CAS  Google Scholar 

  21. He TC, Sparks AB, Rago C et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512

    Article  PubMed  CAS  Google Scholar 

  22. Koh TJ, Bulitta CJ, Fleming JV et al (2000) Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis. J Clin Invest 106:533–539

    Article  PubMed  CAS  Google Scholar 

  23. Yamada T, Takaoka AS, Naishiro Y et al (2000) Transactivation of the multidrug resistance 1 gene by T-cell factor 4/beta-catenin complex in early colorectal carcinogenesis. Cancer Res 60:4761–4766

    PubMed  CAS  Google Scholar 

  24. Crawford HC, Fingleton BM, Rudolph-Owen LA et al (1999) The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 18:2883–2891

    Article  PubMed  CAS  Google Scholar 

  25. Kolligs FT, Bommer G, Goke B et al (2002) Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 66:131–144

    Article  PubMed  CAS  Google Scholar 

  26. Ebert MP, Fei M, Kahmann S et al (2002) Increased beta-catenin mRNA levels and mutational alterations of the APC and beta-catenin gene are present in intestinal-type gastric cancer. Carcinogenesis 23:87–91

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Professor Jiliang Fu (Department of Medicine and Life Sciences, Tongji University, Shanghai 200092, China) and Zhimin He (Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, China) for their constructive comments of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shui-Liang Wang.

Additional information

Grants support: Grants 2004J067 from the Young Scientific and Technical Innovation Foundation of Fujian Province, C0710038 from the Natural Science Foundation of Fujian Province of China, and 200638 from the Foundation of Fuzhou Dongfang Hospital.

The authors Shui-Liang Wang and De-Zhu Zheng contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, SL., Zheng, DZ., Lan, FH. et al. Increased expression of hLRH-1 in human gastric cancer and its implication in tumorigenesis. Mol Cell Biochem 308, 93–100 (2008). https://doi.org/10.1007/s11010-007-9616-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9616-1

Keywords

Navigation