A TIMP-1 splice variant transcript: possible role in regulation of TIMP-1 expression

Cancer Lett. 2008 Apr 8;262(1):64-70. doi: 10.1016/j.canlet.2007.11.030. Epub 2008 Jan 3.

Abstract

A splice variant of tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA lacking exon 2 (TIMP-1-v2) has been identified in human cancer cells and in colorectal and breast cancer tumors. The purpose of this study was (1) to study the level of full length TIMP-1 and TIMP-1-v2 transcripts in colorectal tumors; (2) to investigate if TIMP-1-v2 is translated to protein. Full length TIMP-1 and TIMP-1-v2 mRNA levels were compared between colorectal tumors and normal mucosa by Q-PCR. Both full length TIMP-1 and TIMP-1-v2 transcripts were upregulated in tumor tissue. However, the level of TIMP-1-v2 relative to full length TIMP-1 was higher in normal compared to tumor tissue. Translation of TIMP-1-v2 to protein was analyzed in CHO cells. In this system, no TIMP-1-v2 protein was produced. Thus, the variant transcript seems to be an untranslated mRNA. These findings suggest that alternative splicing of TIMP-1 pre-mRNA to TIMP-1-v2 mRNA might be involved in regulating TIMP-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Animals
  • Colon / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Cricetinae
  • Cricetulus
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intestinal Mucosa
  • Protein Isoforms*
  • RNA, Messenger / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1