Hath1, down-regulated in colon adenocarcinomas, inhibits proliferation and tumorigenesis of colon cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2004-09, Vol.64 (17), p.6050-6057
• Main Authors: CHING CHING LEOW, ROMERO, Maria S, ROSS, Sarajane, POLAKIS, Paul, GAO, Wei-Qiang
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Antineoplastic agents; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Cell Adhesion - physiology; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - genetics; Cell Differentiation - physiology; Cell Division - physiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cyclin D1 - biosynthesis; Cyclin D1 - genetics; Cyclin-Dependent Kinase Inhibitor p27; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Down-Regulation; Gene Expression Regulation, Neoplastic; Goblet Cells - metabolism; Goblet Cells - pathology; HT29 Cells; Humans; Medical sciences; Mice; Mice, Nude; Mucin-2; Mucins - biosynthesis; Pharmacology. Drug treatments; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - physiology; Signal Transduction; Transfection; Transplantation, Heterologous; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Tumors; Wnt Proteins
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-04-0290

A striking feature of colon tumors is the significant reduction of goblet cells. Although targeted deletion of Math1 in mice leads to a loss of intestinal secretory cells, including goblet cells, the role of Hath1 in colon tumorigenesis remains unknown. Here we report that Hath1, the human ortholog of Math1, was dramatically down-regulated in colon tumor samples and colon cancer cell lines. Overexpression of Hath1 in HT29, an aggressive colon cancer cell line, resulted in a significant inhibition on cell proliferation, anchorage-independent growth in soft agar and, more importantly, growth of human colon cancer cell xenografts in athymic nude mice. Such inhibition was accompanied by altered expression of a goblet cell differentiation marker, MUC2, and cell cycle regulators cyclin D1 and p27kip1. Hath1 expression also was up-regulated on inhibition of the Wnt pathway, which has been well implicated in colon tumorigenesis. Hence, this study suggests that Hath1 may be a novel factor downstream of the Wnt pathway capable of suppressing anchorage-independent growth of colon cancer cell lines. More importantly, this study is the first to establish a link between down-regulation of Hath1 expression and colon tumorigenesis.