Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Hath1 Inhibits Proliferation of Colon Cancer Cells Probably Through Up-regulating Expression of Muc2 and p27 and Down-regulating Expression of Cyclin D1

  • Zhu, Dai-Hua (Department of General Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Niu, Bai-Lin (Department of Emergency, the First Affiliated Hospital of Chongqing Medical University) ;
  • Du, Hui-Min (Department of Oncology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Ren, Ke (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Sun, Jian-Ming (Department of General Surgery, the Second Affiliated Hospital of Chongqing Medical University) ;
  • Gong, Jian-Ping (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
  • Published : 2012.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

Keywords

References

  1. Akazawa C, Ishibashi M, Shimizu C, et al (1995). A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system. J Biol Chem, 270, 8730-8. https://doi.org/10.1074/jbc.270.15.8730
  2. Bermingham NA, Hassan BA, Price SD, et al (1999). Math1: an essential gene for the generation of inner ear hair cells. Science, 284, 1837-41. https://doi.org/10.1126/science.284.5421.1837
  3. Blok P, Craanen ME, Van Diest PJ, et a1 (2000). Lack of cyc1in D1 overexpression in gastric carcinogenesis. Histopathology, 36, 151-55. https://doi.org/10.1046/j.1365-2559.2000.00798.x
  4. Bryja V, Pachernik J, Faldikova L, et al (2004). The role of p27(Kip1) in maintaining the levels of D-type cyclins in vivo. Biochim Biophys Acta, 1691, 105-16. https://doi.org/10.1016/j.bbamcr.2004.01.001
  5. Fritzsch B, Matei VA, Nichols DH, et al (2005). Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention. Dev Dyn, 33, 570-83.
  6. Gazit R, Krizhanovsky V, Ben-Arie N (2004). Math1 controls cerebellar granule cell differ- entiation by regulating multiple components of the Notch signaling pathway. Development, 131, 903-13. https://doi.org/10.1242/dev.00982
  7. Grady WM (2004). Genomic instability and colon cancer. Cancer Metastasis Rev, 23, 11-27. https://doi.org/10.1023/A:1025861527711
  8. Hamilton SR(1992). The adenoma-adenocarcinoma sequence in the large bowel: varia- tion on a theme. J Cell Biochem, 16, 41-46.
  9. Hanski C, Riede E, Gratchev A, et al (1997). MUC2 gene suppression in human colo- rectal carcinomas and their metastases: in vitro evidence of the modulatory role of DNA methylation. Lab Invest, 77, 685-95.
  10. Jones J.M, Montcouquiol M, Dabdoub A, et al (2006). Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Cort. J Neurosci, 26, 550-58. https://doi.org/10.1523/JNEUROSCI.3859-05.2006
  11. Kang YK, Kim WH, Jang JJ (2002). Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb)and Smad4/Dpe4 in intrahepatic cholangiocareinoma. Hum Patho L, 33, 877-83. https://doi.org/10.1053/hupa.2002.127444
  12. Kawamoto K, Ishimoto S, Minoda R, et al (2003). Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci, 23, 4395-400.
  13. Leow CC, Romero SS, Ross S, et al (2004). Hath1, Down- Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells. Cancer Res, 64, 6050-57. https://doi.org/10.1158/0008-5472.CAN-04-0290
  14. Liu JJ, Shin JH, HyrcKL, et al (2006). Stem cell therapy for hearing loss: Math1 overexpression in VOT-E36 cells. Otol Neurotol, 27, 414-21. https://doi.org/10.1097/00129492-200604000-00020
  15. Loda M, Cukor B, Tam SW, et al (1997). Increased proteasomedependent degradation of the cyclin-dependent kinase inhibitor p27kipl in aggressive colorectal carcinomas. Nat Med, 3, 231-234. https://doi.org/10.1038/nm0297-231
  16. Markowitz SD, Dawson DM, Willis J, et al (2002). Focus on colon cancer. Cancer Cell, 1, 233-6. https://doi.org/10.1016/S1535-6108(02)00053-3
  17. Newland RC, Dent OF, Lyttle M NB, et al (1999). Pathological determinants of surviva1 associated with colorectal cancer with lymph node metastases. A multivariate analysis of 579 patients. Cancer, 85, 2076-2079
  18. Park E.T, Oh HK, Gum JR Jr, et al (2006). Hath1 expression in mucinous cancers of the colorectum and related lesions. Clin Cancer Res, 12, 5403-10. https://doi.org/10.1158/1078-0432.CCR-06-0573
  19. Park MS, Rosai J, Nguyen HT, et al (1999). p27 and Rb are on overlapping pathways suppressing tumorigenesis in mice. Proc Natl Acad Sci USA, 96, 6382-7. https://doi.org/10.1073/pnas.96.11.6382
  20. Pinto D, Gregorieff A, Begthel H, et al (2003). Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev, 17, 1709-13. https://doi.org/10.1101/gad.267103
  21. Ponz de Leon M, Di Gregorio C (2001). Pathology of colorectal cancer. Dig Liver Dis, 33, 372-88. https://doi.org/10.1016/S1590-8658(01)80095-5
  22. Sherr CJ (1996). Cancer cell cyde. Science, 274, 1672-7. https://doi.org/10.1126/science.274.5293.1672
  23. Shin A, Li H, Shu XO, et al (2006). Dietary intake of calcium, fiber and other micronutrients in relation to colorectal cancer risk: Results from the Shanghai Women's Health Study. Int J Cancer, 119, 2938-42. https://doi.org/10.1002/ijc.22196
  24. Shou J, Zheng JL, Gao WQ (2003). Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1. Mol Cell Neurosci, 23, 169-79 https://doi.org/10.1016/S1044-7431(03)00066-6
  25. Slingerland J, Pagano M (2000). Regulation of the CDK inhibitor p27 and its deregu- lation in cancer. J Cell Physiol, 183, 10-7. https://doi.org/10.1002/(SICI)1097-4652(200004)183:1<10::AID-JCP2>3.0.CO;2-I
  26. Staecker H, Praetorius M, Baker K, et al (2007). Vestibular hair cell regeneration and restoration of balance function induced by Math1 gene transfer. Otol Neurotol, 28, 223-31. https://doi.org/10.1097/MAO.0b013e31802b3225
  27. Toncheva D, Petrova D, Tzenova V, et al (2004). Tissue M icroarray Analysis of Cyclin D1 Gene Amplification and Gain in Colorectal Carcinomas. Tumor Biology, 25, 157-160 https://doi.org/10.1159/000081097
  28. Wong WM, Mandir N, Goodlad RA, et al (2002). Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission. Gut, 50, 212-17. https://doi.org/10.1136/gut.50.2.212
  29. van de Wetering M, Sancho E, Verweij C, et al (2002). The $\beta$-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell, 111, 241-50. https://doi.org/10.1016/S0092-8674(02)01014-0
  30. Velcich A, Yang W, Heyer J, et al (2002). Colorectal cancer in mice genetically deficient in the mucin Muc2. Science, 295, 1726-29. https://doi.org/10.1126/science.1069094
  31. Yang Q, Bermingham NA, Finegold MJ, et al (2001). Requirement of Math1 for secre- tory cell lineage commitment in the mouse intestine. Science, 294, 2155-58. https://doi.org/10.1126/science.1065718
  32. Yang W, Velcich A, Lozonschi I, et al (2005). Inactivation of p21WAF1/cip1 enhances intestinal tumor formation in Muc2- /-mice. Am J Pathol, 166, 1239-46. https://doi.org/10.1016/S0002-9440(10)62342-5
  33. Zheng JL, Gao WQ (2000). Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat Neurosci, 3, 580-86. https://doi.org/10.1038/75753

Cited by

  1. Effect of Hath1 on the proliferation and apoptosis of cutaneous squamous cell carcinoma in vitro vol.12, pp.6, 2015, https://doi.org/10.3892/mmr.2015.4463