Tumor Metastasis-Associated Human Mtal Gene: Role in Epithelial Cancer Cell Proplieration and Regulation

Abstract

Using homology to the rat mta1 gene we cloned the human MTA1 gene. We found a close similarity between the human MTA1 and rat mta1 genes and their predicted amino acid sequences. Both genes encode novel proteins that contain a proline rich region (SH3 binding motif), a putative zinc finger motif, a leucine zipper motif and 5 copies of the SPXX motif often found in gene regulatory proteins. Using Southern blot analysis the MTA1 gene was found to be highly conserved among all species examined, and using Northern blot analysis MTA1 transcripts were found in virtually all cell lines of human origin that were analyzed, including melanoma and breast, cervix and ovarian carcinoma cells and normal breast epithelial cells. However, the expression level of the MTA1 gene in rapidly growing human cell lines and normal breast epithelial cells was approximately 50% of that found in metastatic cell lines and invasive and metastatic tumors. Tumors that over-expressed MTA1 RNA showed significantly higher rates of invasion and lymph node metastasis and tended to have higher rates of vascular involvement.