NUCLEOTIDE EXCISION REPAIR IS ELEVATED IN COMMERCIALLY AVAILABLE LATE STAGE BREAST CANCER CELL LINES AS COMPARED TO EARLY STAGE EXPLANTS

Melnick Auditorium

Objective. To determine functional nucleotide excision repair (NER) capacity and relative NER gene expression in a series of commonly used stage IV breast cancer-derived cell lines relative to stage I breast tumor and non-diseased breast reduction primary cultures. Background. Genomic instability is a hallmark of human carcinogenesis. Sporadic stage I breast tumors exhibit deficient NER capacity relative to non-diseased breast reduction primary cultures. We investigated whether this feature of early human breast cancer is maintained in cell lines established from late stage tumors. Methods. NER function was determined using the unscheduled DNA synthesis assay in six established breast cancer cell lines. JL BTL-12, derived from a stage III breast tumor, was included to represent an advanced stage tumor cell line established in our culture system. These cultures were compared to 23 non-diseased breast reduction and 19 stage I breast tumor primary cultures. NER gene expression was determined by gene expression microarray in 5 established cell lines, JL BTL-12 and representatives of normal (JL BRL-6) and stage I tumor cultures (JL BTL-8). Results. The commercial cell lines and JL BTL-12 had significantly higher NER capacity when compared to stage I tumors. Supervised analysis based on expression of 20 NER genes clustered JL BTL-12 and the five commercial cell lines in one group, while JL BTL-8 and JL BRL-6 clustered together separately. Four NER genes were upregulated significantly in JL BTL-12 and all commercial cell lines relative to JL-BTL-8. Conclusion. Late stage breast tumor cell lines differ significantly from the types of tumors most prevalent at diagnosis. Grants. DOD, NIH, Komen for the Cure.