Genetic Determinants of Breast Cancer Metastasis.
Abstract
The existence of metastatic suppressor genes was originally predicted based on somatic cell hybrid fusions between nonmetastatic and metastatic tumor cells. The resulting hybrids, whil% retaining their tumorigenic potential, were unable to metastasize 1-3. A prostate cancer metastatic suppressor locus was localized on human chromosome 11 in the region lip1 1.2 and was subsequently shown to be KM 1, a leukocyte surface glycoprotein 4. Analysis of murine melanoma and human breast cancer cell lines revealed the specific down regulation of the gene NM23, a nucleoside 5'-phosphate kinase in metastatic tumors or cell lines versus nonmetastatic samples 5. Introduction of E-cadherin cDNAs into tumor cell lines has demonstrated the suppression of metastatic capacity of both mouse and human carcinomas 6-8. Additional evidence for the existence of genes that can suppress metastasis was generated from a series of transfection experiments into murine cells. It was determined that a variety of activated proto-oncogenes, including H-RAS, v-mos, v-raf, A-RAF, v-src, v-fes, v-fms, and p53 could induce primary tumors with metastatic dissemination when transfected NIH-3T3 cells were injected into mice. However, when the same oncogenes were transfected into cell lines derived from different strains of mice, metastatic potential, but not tumorigenicity, was lost 9, 10. This suggests that certain alleles present in some of the inbred strains of mice, either alone or in combination, can function as a metastasis suppressor. At present, these loci have yet to be characterized.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA352403
Entities
People
- Kent W Hunter
Organizations
- Fox Chase Cancer Center