FUNCTIONAL EVIDENCE FOR A BREAST-CANCER GROWTH SUPPRESSOR GENE ON CHROMOSOME-17

Rearrangements or deletions of chromosome 17 are the most frequently observed genetic changes identified in breast tumors. Molecular analyses suggest that in addition to the p53 gene on 17p13.1 there may be at least three other tumor suppressor genes on chromosome 17 involved in breast cancer. Regions of loss of heterozygosity (LOH) identified on 17p13.3 and 17q12-qter occur frequently in breast tumors, and the BRCA-1 gene has been mapped to 17q21 by genetic linkage analysis. Here we provide biological evidence for the presence of a growth suppressor gene(s) on chromosome 17 that results in the in vitro growth suppression of the p53 wild-type MCF 7 breast cancer cell line. We have introduced a normal chromosome 17 into MCF 7 cells by microcell-mediated chromosome transfer (MMCT), and demonstrate that cells growth arrest before 10 to 12 population doublings. In contrast, the introduction of a normal chromosome 13 had no effect upon growth of these cells either in vitro or in vivo. These data provide direct functional evidence for the presence of a growth suppressor gene(s) on chromosome 17, which is not p53, and which may represent one of several gene(s) that play a critical role in the development of breast cancer.