Abstract 1717: SATB1 expression increases resistance of bladder cancer cells to cisplatin

Abstract Background: SATB1 (special AT-rich sequence binding protein-1) is a nuclear protein involved in chromatin organization and gene regulation. Increased expression of SATB1 in breast and hepatocellular cancer cells has been shown to promote metastasis and multidrug resistance. We explored the effects of SATB1 expression in the high grade human bladder cancer cell line, HTB-5. Methods: HTB-5 cells were transfected with an shRNA construct for SATB1 or a non-silencing (NS) control. Nuclear protein and mRNA expression were measured by Western analysis and real-time PCR, respectively. Cells were counted on days 2-6 of culture, and DNA replication was measured by thymidine incorporation (TdR) on day 3. Cell cycle distribution and cell viability were analyzed by propidium iodide-Annexin V FITC flow cytometry in 3 independent experiments. Cells were treated with cisplatin (6 μM) for 3 days. Results: SATB1 mRNA and protein expression levels were 28-fold and 5-fold higher, respectively, in HTB-5 cells compared to UROtsa cells, a benign transformed human urothelial cell line. Expression of SATB1 was reduced 80% or more in shRNA transfected HTB-5 cells. Cell counts and TdR were decreased 20-23% (p<0.01) in SATB1 knockdown cells compared to NS controls. SATB1 knockdown was associated with a significant increase of 15% in G1/G0 and decrease of 18% in S-phase. There was no significant difference in cell viability between SATB1 knockdown cells and NS controls. However, cisplatin treatment resulted in a decrease in live cells from 61.9 ± 4.6% to 39.5 ± 5% (p<0.01) and an increase in apoptotic cells from 33.1 ± 4.4% to 56.1 ± 4.0% (p<0.01) in SATB1 knockdown cells compared to NS controls. Conclusions: SATB1 expression was higher in a malignant compared to benign urothelial cell line and was associated with increased proliferation and increased resistance to chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1717. doi:10.1158/1538-7445.AM2011-1717