PURPOSE: The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells. METHODS: The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells was measured, and inhibitory study using various organic anions on estrone-3-sulfate uptake by MCF-7 cells was conducted. The effects of the inhibitor on the transcription of reporter gene and cell proliferation induced by estrone-3-sulfate were examined. RESULTS: The uptake of estrone-3-sulfate by MCF-7 cells was saturable with Km value of 2.32 microM. The uptake was Na+-independent and was inhibited by several anionic compounds such as bromosulfophthalein. Bromosulfophthalein also significantly inhibited the transcription of reporter gene via estrogen response element and cell proliferation induced by estrone-3-sulfate. However, the transcriptional activation or cell proliferation induced by estrone was not inhibited by bromosulfophthalein. Reverse transcription-polymerase chain reaction analysis revealed the expression of mRNA of organic anion transporting polypeptide (OATP)-D and OATP-E as possible candidates to transport estrone-3-sulfate. CONCLUSIONS: The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.
PURPOSE: The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells. METHODS: The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells was measured, and inhibitory study using various organic anions on estrone-3-sulfate uptake by MCF-7 cells was conducted. The effects of the inhibitor on the transcription of reporter gene and cell proliferation induced by estrone-3-sulfate were examined. RESULTS: The uptake of estrone-3-sulfate by MCF-7 cells was saturable with Km value of 2.32 microM. The uptake was Na+-independent and was inhibited by several anionic compounds such as bromosulfophthalein. Bromosulfophthalein also significantly inhibited the transcription of reporter gene via estrogen response element and cell proliferation induced by estrone-3-sulfate. However, the transcriptional activation or cell proliferation induced by estrone was not inhibited by bromosulfophthalein. Reverse transcription-polymerase chain reaction analysis revealed the expression of mRNA of organic anion transporting polypeptide (OATP)-D and OATP-E as possible candidates to transport estrone-3-sulfate. CONCLUSIONS: The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.
Authors: T Abe; M Unno; T Onogawa; T Tokui; T N Kondo; R Nakagomi; H Adachi; K Fujiwara; M Okabe; T Suzuki; K Nunoki; E Sato; M Kakyo; T Nishio; J Sugita; N Asano; M Tanemoto; M Seki; F Date; K Ono; Y Kondo; K Shiiba; M Suzuki; H Ohtani; T Shimosegawa; K Iinuma; H Nagura; S Ito; S Matsuno Journal: Gastroenterology Date: 2001-06 Impact factor: 22.682
Authors: Juma Hoshino; Eun-Jung Park; Tamara P Kondratyuk; Laura Marler; John M Pezzuto; Richard B van Breemen; Shunyan Mo; Yongchao Li; Mark Cushman Journal: J Med Chem Date: 2010-07-08 Impact factor: 7.446
Authors: Jonathan L Wright; Erika M Kwon; Elaine A Ostrander; R Bruce Montgomery; Daniel W Lin; Robert Vessella; Janet L Stanford; Elahe A Mostaghel Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-01-25 Impact factor: 4.254
Authors: Nilasha Banerjee; T Robert Wu; Jason Chio; Ryan Kelly; Karin A Stephenson; John Forbes; Christine Allen; John F Valliant; Reina Bendayan Journal: Nucl Med Biol Date: 2014-11-08 Impact factor: 2.408
Authors: Wooin Lee; Abbes Belkhiri; A Craig Lockhart; Nipun Merchant; Hartmut Glaeser; Elizabeth I Harris; M Kay Washington; Elizabeth M Brunt; Alex Zaika; Richard B Kim; Wael El-Rifai Journal: Cancer Res Date: 2008-12-15 Impact factor: 12.701
Authors: Henriette E Meyer zu Schwabedissen; Rommel G Tirona; Cindy S Yip; Richard H Ho; Richard B Kim Journal: Cancer Res Date: 2008-11-15 Impact factor: 12.701