Functional evidence for a breast cancer growth suppressor gene on chromosome 17

Rearrangements or deletions of chromosome 17 are the most frequentlyobserved genetic changes identified in breast tumors. Molecularanalyses suggest that in addition to the p53 gene on 17p13.1there may be at least three other tumor suppressor genes onchromosome 17 involved in breast cancer. Regions of loss ofheterozygosity (LOH) identified on 17p13.3 and 17q12-qter occurfrequently in breast tumors, and the BRCA-1 gene has been mappedto 17q21 by genetic linkage analysis. Here we provide biologicalevidence for the presence of a growth suppressor gene(s) onchromosome 17 that results In the In vitro growth suppressionof the p53 wild-type MCF 7 breast cancer cell line. We haveIntroduced a normal chromosome 17 into MCF 7 cells by microcellmediatedchromosome transfer (MMCT), and demonstrate that cells growtharrest before 10 to 12 population doublings. In contrast, theintroduction of a normal chromosome 13 had no effect upon growthof these cells either In vitro or In vivo. These data providedirect functional evidence for the presence of a growth suppressorgene(s) on chromosome 17, which is not p53, and which may representone of several gene(s) that play a critical role in the developmentof breast cancer.