Abstract
Abstract
Genomic instability is a hallmark of human carcinogenesis. We have previously published that sporadic stage I breast tumors exhibit deficient Nucleotide Excision Repair (NER) capacity relative to non-diseased breast reduction primary cultures (Latimer et al., 2010). In the present work, we hypothesized that this feature of early human breast cancer would not be maintained in cell lines established from late stage tumors. Our objective was to determine functional 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 cancer explants and cell lines. NER capacity was determined using the functional unscheduled DNA synthesis (UDS) assay in six established breast cancer cell lines (MCF-7, MCF-7LY2, MDA-MB-231, SK-BR-3, CAMA-1, BT-20). JL BTL-12 (Jean Latimer Breast Tumor Line-12), derived from a stage III breast tumor, was included to represent an advanced stage tumor cell line established using our culture system. The NER capacity of the cell lines was compared to that of 19 stage I breast tumor primary cultures. NER gene expression was determined by expression microarray using the Affymetrix HG U-133 plus 2.0 chip in five of these established cell lines (MCF-7, MDA-MB-231, SK-BR-3, CAMA-1, BT-20), JL BTL-12 and a representative stage I tumor-derived cell line (JL BTL-8, Breast Tumor Line-8). The stage IV cell lines and JL BTL-12 all manifested significantly higher NER capacity than explants of stage I breast cancer. Unsupervised as well as supervised analyses, based on expression of the canonical 20 NER genes, placed JL BTL-12 and the five stage IV commercial cell lines in one cluster, while JL BTL-8 clustered separately. Four NER genes were significantly upregulated in JL BTL-12 and all commercial cell lines relative to JL BTL-8. In conclusion, based on NER these five cell lines commonly used in breast cancer research are more representative of late stage disease than early stage breast cancer, regardless of the type of breast cancer they represent. The most commonly diagnosed stage of breast cancer in the U.S. is now stage I, and it is now possible to study stage I cell lines or explants.
Citation Format: Homood As Sobeai, Jennifer M. Johnson, Nancy Lalanne, Omar Ibrahim, Stephen G. Grant, Sharon L. Wenger, Jean J. Latimer. Nucleotide excision repair is elevated in stage IV commonly used breast cancer cell lines as compared to stage I breast tumor explants. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3589.