Abstract 1816: SULT1A1 gene expression level is correlated with gene copy number in different human epithelial and breast cancer cell lines.

Abstract

Abstract Sulfotransferase isoform 1A1 (SULT1A1) is a member of a subfamily of cytosolic enzymes which catalyze the transfer of a sulfonate group from 3’-phosphoadenosine 5’ -phosphosulfate (PAPS) to a range of xenobiotic and endogenous compounds such as drugs, carcinogens, and steroid hormones. SULT1A1 plays a role in detoxification of tamoxifen (TAM), a drug for estrogen receptor (ER) positive breast cancer treatment and chemoprevention. Besides its involvement in drug metabolism, SULT1A1 also contributes to increased cancer risk. SULT1A1 activity varies several-fold among individuals. Earlier studies have shown that individuals can possess one to five copies of the SULT1A1 gene. SULT1A1 gene expression is higher in individuals with more than one copy number, although there is no significant difference among individuals who have more than 3 copy numbers. We determined the copy number of SULT1A1 in cell lines ZR75, MCF7, T47D, MDA-MB-231, and MCF10A using a pre-designed Custom Plus TaqMan® Copy Number kit from Life Technology. Similar to the human population, the human cell lines tested also contain one to five copies of SULT1A1. Genomic DNA of MCF7, MDA-MB-231, and MCF10A cells contains only one copy of SULT1A1, while ZR75 DNA contains 3 copies and T47D DNA contains 5 copies of SULT1A1. To determine if copy number correlates with gene expression level, we compared the amount of SULT1A1 mRNA by RT-PCR in each cell line with corresponding copy numbers. Cell lines with one copy of SULT1A1 (MCF7 and MCF10A) had lower gene expression; while cell lines with more than one copy number (ZR75 and T47D) had higher gene expression. ZR75 cells expressed significantly more SULT1A1 mRNA than that of T47D, even though ZR75 DNA has two less copies than T47D cells. Although MDA-MB-231 DNA contains one copy of SULT1A1, no SULT1A1 gene expression was detected, indicating that other mechanisms exist in regulating SULT1A1 gene expression. In summary, the current data suggest that differential SULT1A1 gene expression levels in human breast cancer cells could be partially regulated by its copy numbers. Furthermore, the cell lines tested here could be used as in vitro models to study the mechanisms of SULT1A1 gene expression regulations since the copy number differences in those cell lines represented the copy number differences in human population. Citation Format: Aiwei Yao-Borengasser, Lora J. Rogers, Rosalind B. Penny, Vineetha K. Edvana, Susan A. Kadlubar. SULT1A1 gene expression level is correlated with gene copy number in different human epithelial and breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1816. doi:10.1158/1538-7445.AM2013-1816