Journal of Zhejiang University SCIENCE B

, Volume 8, Issue 1, pp 39–44 | Cite as

FoxO4 is the main forkhead transcriptional factor localized in the gastrointestinal tracts of pigs

  • Zhou Zhen-qi 
  • Wang Tian 
  • Pan Ling-mei 
  • Huang Rui-hua 
  • Shi Fang-xiong 


Forkhead box (Fox) proteins play critical roles in the regulation of differentiation, proliferation, immunity and aging of cells. Most studies on Fox proteins are limited to cultured cells and rodent. The aim of the current study is to detect by immunohistrochemistry whether FoxO1, FoxO3a and FoxO4 proteins are localized in the stomach and intestine of the pig. The results showed that FoxO4 exists in the mucosa in all parts of the stomach and intestine; FoxO3a exists mainly in the lamina propria and muscularis of some parts. However, FoxO1 is not detectable in all parts of the stomach and intestine. Collectively, the results of the present study indicate that there exists a distinct expression pattern of Fox proteins, and that FoxO4 is a primary forkhead transcriptional factor localized in the gastrointestinal tracts of the pig.

Key words

Forkhead FoxO Gastrointestinal tract Immunohistochemistry Swine 

CLC number



Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Accili, D., Arden, K.C., 2004. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 117(4):421–426. [doi:10.1016/S0092-8674(04)00452-0]PubMedCrossRefGoogle Scholar
  2. Arden, K.C., Biggs, W.H., 2002. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling. Arch. Biochem. Biophys., 403(2):292–298. [doi:10.1016/S0003-9861(02)00207-2]PubMedCrossRefGoogle Scholar
  3. Barthélémy, C., Henderson, C.E., Pettmann, B., 2004. FoxO3a induces motoneuron death through the Fas pathway in cooperation with JNK. BMC Neurosci., 5(1):48. [doi:10.1186/1471-2202-5-48]PubMedCrossRefGoogle Scholar
  4. Burgering, B.M., Kops, G.J., 2002. Cell cycle and death control: long live forkheads. Trends Biochem. Sci., 27(7):352–360. [doi:10.1016/S0968-0004(02)02113-8]PubMedCrossRefGoogle Scholar
  5. Fernandez de Mattos, S., Essafi, A., Soeiro, I., Pietersen, A.M., Birkenkamp, K.U., Edwards, C.S., Martino, A., Nelson, B.H., Francis, J.M., Jones, M.C., et al., 2004. FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. Mol. Cell Biol., 24(22):10058–10071. [doi:10.1128/MCB.24.22.10058-10071.2004]PubMedCrossRefGoogle Scholar
  6. Finnberg, N., El-Deiry, W.S., 2004. Activating FOXO3a, NF-kappaB and p53 by targeting IKKs: an effective multi-faceted targeting of the tumor-cell phenotype? Cancer Biol. Ther., 3(7):614–616.PubMedCrossRefGoogle Scholar
  7. Fukuoka, M., Daitoku, H., Hatta, M., Matsuzaki, H., Umemura, S., Fukamizu, A., 2003. Negative regulation of forkhead transcription factor AFX (FoxO4) by CBP-induced acetylation. Int. J. Mol. Med., 12(4):503–508.PubMedGoogle Scholar
  8. Graff, P., Amellem, O., Seim, J., Stokke, T., Pettersen, E.O., 2005. The role of p27 in controlling the oxygen-dependent checkpoint of mammalian cells in late G1. Anticancer Res., 25(3B):2259–2267.PubMedGoogle Scholar
  9. Hoekman, M.F., Jacobs, F.M., Smidt, M.P., Burbach, J.P., 2006. Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr. Patterns, 6(2):134–140. [doi:10.1016/j.modgep.2005.07.003]PubMedCrossRefGoogle Scholar
  10. Hosaka, T., Biggs, W.H.3rd, Tieu, D., 2004. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc. Natl. Acad. Sci. USA, 101(9):2975–2980. [doi:10.1073/pnas.0400093101]PubMedCrossRefGoogle Scholar
  11. Hu, M.C., Lee, D.F., Xia, W., Golfman, L.S., Ou-Yang, F., Yang, J.Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al., 2004. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell, 117(2):225–237. [doi:10.1016/S0092-8674(04)00302-2]PubMedCrossRefGoogle Scholar
  12. Jacobs, F.M., van der Heide, L.P., Wijchers, P.J., Burbach, J.P., Hoekman, M.F., Smidt, M.P., 2003. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics. J. Biol. Chem., 278(38):35959–35967. [doi:10.1074/jbc.M302804200]PubMedCrossRefGoogle Scholar
  13. Kobayashi, Y., Furukawa-Hibi, Y., Chen, C., Horio, Y., Isobe, K., Ikeda, K., Motoyema, N., 2005. SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. Int. J. Mol. Med., 16(2):237–243.PubMedGoogle Scholar
  14. Li, X., Jiang, Y., Wang, Z., Liu, G., Hutz, R.J., Liu, W., Shi, F., 2005a. Regulation of FoxO1 transcription factor by nitric oxide and cyclic GMP in cultured rat granulosa cells. Zool. Sci., 22(12):1339–1346. [doi:10.2108/zsj.22.1339]PubMedCrossRefGoogle Scholar
  15. Li, X., Xie, Z., Shi, F., 2005b. Involvement of forkhead box proteins in apoptosis and oncogenesis. Prog. Biochem. Biophs., 32(7):600–606.Google Scholar
  16. Li, X., Xie, Z., Shi, F., 2006. FOXO in the regulation of differentiation, proliferation, immunity and aging of cells. Chin. J. Clin. Rehabil., 10(9):158–162.Google Scholar
  17. Liu, Y., Lehmann, M., 2006. FOXO-independent suppression of programmed cell death by the PI3K/Akt signaling pathway in Drosophila. Dev. Genes Evol., 216(9):531–535. [doi:10.1007/s00427-006-0063-x]PubMedCrossRefGoogle Scholar
  18. Martinez-Gac, L., Marques, M., Garcia, Z., Campanero, M.R., Carrera, A.C., 2004. Control of cyclin G2 mRNA expression by forkhead transcription factors: novel mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead. Mol. Cell. Biol., 24(5):2181–2189. [doi:10.1128/MCB.24.5.2181-2189.2004]PubMedCrossRefGoogle Scholar
  19. Michl, P., Downward, J., 2005. PI3K/AKT signaling in gastrointestinal cancers. Z. Gastroenterol., 43(10):1133–1139. [doi:10.1055/s-2005-858638]PubMedCrossRefGoogle Scholar
  20. Seoane, J., Le, H.V., Shen, L., Anderson, S.A., Massague, J., 2004. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell, 117(2):211–223. [doi:10.1016/S0092-8674(04)00298-3]PubMedCrossRefGoogle Scholar
  21. Shi, F., LaPolt, P.S., 2003. Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary. J. Endocrinol., 179(2):195–203. [doi:10.1677/joe.0.1790195]PubMedCrossRefGoogle Scholar
  22. Skurk, C., Izumiya, Y., Maatz, H., Razeghi, P., Shiojima, I., Sandri, M., Sato, K., Zeng, L., Schiekofer, S., Pimentel, D., et al., 2005. The FoxO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J. Biol. Chem., 280(21):20814–20823. [doi:10.1074/jbc.M500528200]PubMedCrossRefGoogle Scholar
  23. Stahl, M., Dijkers, P.F., Kops, G.J., Lens, S.M., Coffer, P.J., Burgering, B.M., Medema, R.H., 2002. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J. Immunol. (Baltimore, Md.: 1950), 168(10):5024–5031.Google Scholar
  24. Wang, T., Huo, Y.J., Shi, F., Xu, R.J., Hutz, R.J., 2005. Effects of intrauterine growth retardation on development of the gastrointestinal tract in neonatal pigs. Biol. Neonate, 88(1):66–72. [doi:10.1159/000084645]PubMedCrossRefGoogle Scholar
  25. Weinkove, D., Halstead, J.R., Gems, D., Divecha, N., 2006. Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FoxO to the cytoplasm. BMC Biol., 4(1):1. [doi:10.1186/1741-7007-4-1]PubMedCrossRefGoogle Scholar
  26. Yamamura, Y., Lee, W.L., Inoue, K., Ida, H., Ito, Y., 2006. RUNX3 cooperates with FOXO3a to induce apoptosis in gastric cancer cells. J. Biol. Chem., 281(8):5267–5276. [doi:10.1074/jbc.M512151200]PubMedCrossRefGoogle Scholar
  27. Yang, H., Zhao, R., Yang, H.Y., Lee, M.H., 2005. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. Oncogene, 24(11):1924–1935. [doi:10.1038/sj.onc.1208352]PubMedCrossRefGoogle Scholar
  28. Zhang, D.W., Li, X.Y., Chen, L.T., 2001. Animal models and pathological changes in gastroesophageal reflux. Chin. J. Pediatr. Surg., 22(2):112–114.Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Zhou Zhen-qi 
    • 1
  • Wang Tian 
    • 1
  • Pan Ling-mei 
    • 1
  • Huang Rui-hua 
    • 1
  • Shi Fang-xiong 
    • 1
  1. 1.College of Animal Science and TechnologyNanjing Agricultural UniversityNanjingChina

Personalised recommendations