The differences in PEDF expression between BT474, MCF 7,5C, and MCF 7,2A cells might possibly be influenced by the different signaling pathways that control the resistant phenotype of these cells. The ERa protein level was also examined in the differ ent cell lines to assess whether there was a correlation between www.selleckchem.com/products/Belinostat.html ERa status and PEDF expression. Figure 1a showed that ERa protein was expressed in all of the cell lines except for MDA MB 231 cells, which are ERa negative, however, ERa was significantly elevated in endocrine resistant MCF 7,5C, MCF 7,2A, and BT474 cells compared with endocrine sensitive MCF 7, T47D, and ZR 75 1 cells. In addition, we found that E2 treat ment markedly reduced the PEDF protein level in MCF 7 and T47D cells whereas 4OHT, the active metabolite of tamoxifen, significantly increased the PEDF protein level in both cell lines.

A similar trend was observed for ERa regulation by E2 and 4OHT in MCF 7 and T47D cells. Overall, these data show that PEDF expression is significantly reduced in endocrine resistant breast cancer cells compared with endocrine sensitive cells and that its expression is differentially regulated by estrogen and anti Inhibitors,Modulators,Libraries estrogen in hormone dependent breast cancer cells. No significant correlation, however, was observed between PEDF expression and total ERa status. PEDF expression is dramatically reduced in endocrine resistant breast tumors Since PEDF expression was dramatically reduced in endo crine resistant breast cancer cells, we next determined whether there was a clinical correlation between PEDF expression and the development of endocrine resistance in breast tumors.

PEDF expression was examined in pri mary versus recurrence tumors. A total of 209 breast can cer patients were initially treated with tamoxifen and responded, however, 59 patients developed recurrence disease with an average time to disease progression of 93 months. Immunohistochemical staining was performed on tissue microarrays constructed using recurrence breast Inhibitors,Modulators,Libraries tumor tissues versus matched primary breast tumor tissues. Figure 2a shows that PEDF protein was dramatically reduced in the recurrence Inhibitors,Modulators,Libraries breast cancer tissue compared with the primary breast cancer tissue and the normal breast tissue . In particular, we found in the normal breast tissue and to a lesser extent Inhibitors,Modulators,Libraries in the primary breast cancer Inhibitors,Modulators,Libraries tissue that mammary epithelial cells displayed an intense and widespread staining for PEDF.

All of the normal breast tissue stained positive for PEDF, whereas 68% of primary tumors were PEDF positive and 32. 2% were PEDF negative. In contrast, we found that 47. 6% of recur rence tumors were PEDF positive and 52. 4% of recurrence tumors were PEDF negative. The number of recurrence tumors that were PEDF nega tive was statistically significantly different selleck catalog from the num ber of primary tumors that were PEDF negative.