Growth Suppressors of Breast Cancer Cells

A genetic system has been established for the isolation of candidate tumor suppressor genes in MCF7 breast cancer cells. This system includes the IPTG-inducible episomal vector, which combines the advantages of inducible expression systems and extra-chromosomal replication systems. A cDNA library from normal human breast epithelial cells was constructed in the pEpiLac vector system, and transfected into a cell line (LAP 5) derived from the human breast cancer MCF7 cells which allows the inducible expression of the library DNA. After several rounds of selections of 6,000 independent cDNA clones, 12 sequences that confer growth inhibitory effects on LAPS cells were isolated. Sequence analysis revealed that some of these sequences are fragments of known genes, while others represent novel gene sequences with no known functions. One growth inhibitory cDNA analyzed revealed a novel gene, bop1, which encodes a previously unknown nucleolar protein that is involved in the processing of the 28S and 5.8S rRNA and in the biogenesis of the 60S ribosome. Further analysis of bop1 may lead understanding the cross-talk mechanism between rRNA processing and cell cycle progression.