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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

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

colon carcinoma;etiology;colon carcinoma cell line;cell cycle regulation

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