Rapamycin induces Smad activity in prostate cancer cell lines.
作者： H. van der Poel , C. Hanrahan , H. Zhong , J. Simons
DOI: 10.1007/S00240-002-0282-1
关键词:
摘要: Rapamycin inhibits the FK506-binding protein 12 (FKBP12)/mammalian target of rapamycin (mTOR) complex and causes cell cycle arrest in G1. The precise mechanism growth inhibition by is only partly understood. led to human prostate cancer lines LNCaP PC3 cells after 72 h, ID50: 93 50 nM, respectively. Filter cDNA array analysis showed down-regulation more than 0.75× following genes: follistatin, eukaryotic initiation factor-4E (eIF4E), glucose-6-phosphate dehydrogenase (GAPDH), lactate (LDH)-A, ATP synthase, heat shock (HSP)-1. Upregulation 1.5× was found for: bone morphogenetic (BMP)-4, FKBP12, carcinoma embryonic antigen (CEA) precursor, factor (eIF)-3 p36 subunit, latent transforming (TGF) beta binding (LTBP)1. induced BMP4 reduced follistatin expression cells. This resulted a dose-dependent nuclear Smad4 activated SBE4 Smad-reporter, indicating activation TGFbeta/BMP signaling. Combining with PI3K (LY294002) increased inhibition. These findings illustrate that Smad signaling plays role anticancer effects show combination improves
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Carl-Henrik Heldin, Kohei Miyazono, Peter ten Dijke, TGF-beta signalling from cell membrane to nucleus through SMAD proteins Nature. ,vol. 390, pp. 465- 471 ,(1997) , 10.1038/37284
Natalia Rioseco-Camacho, Faton Agani, William B Isaacs, Gregg L Semenza, Hua Zhong, Jonathan W Simons, Angelo A. Baccala Jr Md, Erick Laughner, Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer. Cancer Research. ,vol. 58, pp. 5280- 5284 ,(1998)
Tobias Schmelzle, Michael N Hall, TOR, a Central Controller of Cell Growth Cell. ,vol. 103, pp. 253- 262 ,(2000) , 10.1016/S0092-8674(00)00117-3
Frank McCormick, ras GTPase activating protein: signal transmitter and signal terminator. Cell. ,vol. 56, pp. 5- 8 ,(1989) , 10.1016/0092-8674(89)90976-8
K. Podsypanina, R. T. Lee, C. Politis, I. Hennessy, A. Crane, J. Puc, M. Neshat, H. Wang, L. Yang, J. Gibbons, P. Frost, V. Dreisbach, J. Blenis, Z. Gaciong, P. Fisher, C. Sawyers, L. Hedrick-Ellenson, R. Parsons, An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/− mice Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 10320- 10325 ,(2001) , 10.1073/PNAS.171060098
Asavari Wagle, Sanjay Jivraj, Ginny L. Garlock, Susan R. Stapleton, Insulin Regulation of Glucose-6-phosphate Dehydrogenase Gene Expression Is Rapamycin-sensitive and Requires Phosphatidylinositol 3-Kinase Journal of Biological Chemistry. ,vol. 273, pp. 14968- 14974 ,(1998) , 10.1074/JBC.273.24.14968
Stephen J. McPherson, Sally L. Mellor, Hong Wang, Lee W. Evans, Nigel P. Groome, Gail P. Risbridger, Expression of activin A and follistatin core proteins by human prostate tumor cell lines. Endocrinology. ,vol. 140, pp. 5303- 5309 ,(1999) , 10.1210/ENDO.140.11.7141
Yiling Lu, Yue-Zhen Lin, Ruth LaPushin, Bruce Cuevas, Xianjun Fang, Shuang Xing Yu, Michael A Davies, Humera Khan, Tatsuro Furui, Muling Mao, Ralph Zinner, Mien-Chi Hung, Peter Steck, Kathy Siminovitch, Gordon B Mills, The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells Oncogene. ,vol. 18, pp. 7034- 7045 ,(1999) , 10.1038/SJ.ONC.1203183
Hua Zhong, Jonathan W. Simons, Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochemical and Biophysical Research Communications. ,vol. 259, pp. 523- 526 ,(1999) , 10.1006/BBRC.1999.0815
Jerry E Chipuk, Susan C Cornelius, Nicole J Pultz, Joan S Jorgensen, Michael J Bonham, Seong-Jin Kim, David Danielpour, None, The Androgen Receptor Represses Transforming Growth Factor-β Signaling through Interaction with Smad3 Journal of Biological Chemistry. ,vol. 277, pp. 1240- 1248 ,(2002) , 10.1074/JBC.M108855200