Abstract

We searched for metastasis-related genes in adenoid cystic carcinoma by suppression subtractive hybridization analysis of high and low metastasis cell lines. Twelve genes (ten previously identified and two novel sequences) were identified as being expressed at lower levels in high metastasis cell line Acc-M when compared to low metastasis cell line Acc-2. The known sequences corresponded to the genes for cysteine-rich angiogenesis induction factor (cyr61), chromosome 7 RP11-52501 clone, G-protein, WAS familial ferritin I heavy chain, jumping translocation breakpoint, eukaryotic translation elongation, folate receptor and three ribosomal proteins. Among them, the G protein and ferritin I heavy chain genes contained mutations in the high metastasis cell line. The two novel gene sequences have been named ACC metastasis-associated RNH and ACC metastasis-associated suspected protein (GenBank # AF522024 and AF522025, respectively). Taken together, these results suggest that reduced expression and/or mutation of several genes in the tumor cell line Acc-M are associated with high tumor metastasis, providing important molecular biological materials for further study of metastasis control and possible targets for cancer gene therapy.

Highlights

  • Metastasis and invasion are important, complex characteristics of malignant tumors (Fang et al, 2001)

  • We report the use of a genetic comparison of two highand low metastasis adenoid cystic carcinoma cell lines as a strategy for identification of tumor metastasis-related genes

  • Adenoid cystic carcinoma (ACC) is a commonly encountered oral-maxillofacial malignant tumor that is known to metastasize to the lung quite often, the mechanism of this metastasis is unknown

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Summary

Introduction

Metastasis and invasion are important, complex characteristics of malignant tumors (Fang et al, 2001). Vol 35(4), 243- 248, 2003 tive hybridization has been used to clone tumor related genes by comparing tumor and normal cell lines, or by comparing different tumor cell lines (VonStein et al, 1997; Guo et al, 2001) This method has been used to identify the kiss-1 gene as being closely associated with melanoma, to isolate the deme-6 gene from a breast cancer cell line, and to isolate the rbap4p gene from Wilm's tumor (VonStein et al, 1997). At this time, no such screening of high and low metastasis cell lines of adenoid cystic carcinoma has been reported. We sought to examine differential gene expression and metastasis-related genes using Acc-2 and Acc-M as templates for suppression subtractive hybridization

Extraction of cell total RNA
Suppression subtractive hybridization
Sequence analysis and homologous comparison of cloned fragments
Northern blot analysis
Differentially expressed genes and relevant homologous comparisons
Findings
Folate receptor
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