| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Imperial Cancer Research Fund, P. O. Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom
The serine/threonine kinase p70s6k was found to be constitutively phosphorylated in H 69, H 345, and H 510 small cell lung cancer cells as judged by the retarded electrophoretic mobility of both isoforms of this kinase. Pretreatment of H 69, H 345, and H 510 cells with the potent immunosuppressant rapamycin led to p70s6k dephosphorylation in a concentration-dependent manner; half-maximum and maximum effects were achieved at 0.3 and 3 nM rapamycin, respectively. Rapamycin inhibited growth of H 69, H 345, and H 510 cells in liquid culture at similar concentrations to those required for inducing dephosphorylation of p70s6k. Furthermore, rapamycin markedly reduced the basal colony forming ability of H 69, H 345, and H 510 cells in semisolid media. Thus, constitutively phosphorylated/active p70s6k plays an important role in promoting the growth of small cell lung cancer cells. Furthermore, the rapamycin-sensitive p70s6k pathway may provide a novel target for therapeutic intervention in small cell lung cancer.
1 To whom requests for reprints should be addressed. Phone: 44-171-269-3455; Fax: 44-171-269-3417.
Received 6/10/96. Accepted 7/16/96.
This article has been cited by other articles:
|
|
 |
|
  C. A. Granville, R. M. Memmott, J. J. Gills, and P. A. Dennis Handicapping the Race to Develop Inhibitors of the Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Pathway Clin. Cancer Res., February 1, 2006; 12(3): 679 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Adjei and M. Hidalgo Intracellular Signal Transduction Pathway Proteins As Targets for Cancer Therapy J. Clin. Oncol., August 10, 2005; 23(23): 5386 - 5403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Galanis, J. C. Buckner, M. J. Maurer, J. I. Kreisberg, K. Ballman, J. Boni, J. M. Peralba, R. B. Jenkins, S. R. Dakhil, R. F. Morton, et al. Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study J. Clin. Oncol., August 10, 2005; 23(23): 5294 - 5304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nozawa, T. Ohno, Y. Banno, T. Dohjima, K. Wakahara, D.-G. Fan, and K. Shimizu Inhibition of Platelet-derived Growth Factor-induced Cell Growth Signaling by a Short Interfering RNA for EWS-Fli1 via Down-regulation of Phospholipase D2 in Ewing Sarcoma Cells J. Biol. Chem., July 29, 2005; 280(30): 27544 - 27551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Li and B. E. Sumpio Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1591 - H1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Dutcher Mammalian Target of Rapamycin Inhibition Clin. Cancer Res., September 15, 2004; 10(18): 6382S - 6387S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gao, D. C. Flynn, Z. Zhang, X.-S. Zhong, V. Walker, K. J. Liu, X. Shi, and B.-H. Jiang G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells Am J Physiol Cell Physiol, August 1, 2004; 287(2): C281 - C291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Stromberg, A. Dimberg, A. Hammarberg, K. Carlson, A. Osterborg, K. Nilsson, and H. Jernberg-Wiklund Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone Blood, April 15, 2004; 103(8): 3138 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bell, X. Cao, J. A. Moibi, S. R. Greene, R. Young, M. Trucco, Z. Gao, F. M. Matschinsky, S. Deng, J. F. Markman, et al. Rapamycin Has a Deleterious Effect on MIN-6 Cells and Rat and Human Islets Diabetes, November 1, 2003; 52(11): 2731 - 2739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Decker, S. Hipp, I. Ringshausen, C. Bogner, M. Oelsner, F. Schneller, and C. Peschel Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression of cyclin D3, cyclin E, cyclin A, and survivin Blood, January 1, 2003; 101(1): 278 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Goncharova, D. A. Goncharov, A. Eszterhas, D. S. Hunter, M. K. Glassberg, R. S. Yeung, C. L. Walker, D. Noonan, D. J. Kwiatkowski, M. M. Chou, et al. Tuberin Regulates p70 S6 Kinase Activation and Ribosomal Protein S6 Phosphorylation. A ROLE FOR THE TSC2 TUMOR SUPPRESSOR GENE IN PULMONARY LYMPHANGIOLEIOMYOMATOSIS (LAM) J. Biol. Chem., August 16, 2002; 277(34): 30958 - 30967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Dilling, G. S. Germain, L. Dudkin, A. L. Jayaraman, X. Zhang, F. C. Harwood, and P. J. Houghton 4E-binding Proteins, the Suppressors of Eukaryotic Initiation Factor 4E, Are Down-regulated in Cells with Acquired or Intrinsic Resistance to Rapamycin J. Biol. Chem., April 12, 2002; 277(16): 13907 - 13917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. E. Pardo, A. Arcaro, G. Salerno, S. Raguz, J. Downward, and M. J. Seckl Fibroblast Growth Factor-2 Induces Translational Regulation of Bcl-XL and Bcl-2 via a MEK-dependent Pathway. CORRELATION WITH RESISTANCE TO ETOPOSIDE-INDUCED APOPTOSIS J. Biol. Chem., March 29, 2002; 277(14): 12040 - 12046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Dudkin, M. B. Dilling, P. J. Cheshire, F. C. Harwood, M. Hollingshead, S. G. Arbuck, R. Travis, E. A. Sausville, and P. J. Houghton Biochemical Correlates of mTOR Inhibition by the Rapamycin Ester CCI-779 and Tumor Growth Inhibition Clin. Cancer Res., June 1, 2001; 7(6): 1758 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-J. Wu, C. S. Sinclair, J. Paape, J. N. Ingle, P. C. Roche, C. D. James, and F. J. Couch 17q23 Amplifications in Breast Cancer Involve the PAT1, RAD51C, PS6K, and SIGMA1B Genes Cancer Res., October 1, 2000; 60(19): 5371 - 5375. [Abstract] [Full Text]
|
|
|
|
|
|
G. von Wichert, P. M. Jehle, A. Hoeflich, S. Koschnick, H. Dralle, E. Wolf, B. Wiedenmann, B. O. Boehm, G. Adler, and T. Seufferlein Insulin-like Growth Factor-I Is an Autocrine Regulator of Chromogranin A Secretion and Growth in Human Neuroendocrine Tumor Cells Cancer Res., August 1, 2000; 60(16): 4573 - 4581. [Abstract] [Full Text]
|
|
|
|
|
|
B. K. Law, P. Norgaard, and H. L. Moses Farnesyltransferase Inhibitor Induces Rapid Growth Arrest and Blocks p70s6k Activation by Multiple Stimuli J. Biol. Chem., April 6, 2000; 275(15): 10796 - 10801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grewe, F. Gansauge, R. M. Schmid, G. Adler, and T. Seufferlein Regulation of Cell Growth and Cyclin D1 Expression by the Constitutively Active FRAP-p70s6K Pathway in Human Pancreatic Cancer Cells Cancer Res., August 1, 1999; 59(15): 3581 - 3587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Louro, P. McKie-Bell, H. Gosnell, B. C. Brindley, R. P. Bucy, and J. M. Ruppert The Zinc Finger Protein GLI Induces Cellular Sensitivity to the mTOR Inhibitor Rapamycin Cell Growth Differ., July 1, 1999; 10(7): 503 - 516. [Abstract] [Full Text]
|
|
|
|
|
|
L. Paolucci and E. Rozengurt Protein Kinase D in Small Cell Lung Cancer Cells: Rapid Activation through Protein Kinase C Cancer Res., February 1, 1999; 59(3): 572 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hosoi, M. B. Dilling, T. Shikata, L. N. Liu, L. Shu, R. A. Ashmun, G. S. Germain, R. T. Abraham, and P. J. Houghton Rapamycin Causes Poorly Reversible Inhibition of mTOR and Induces p53-independent Apoptosis in Human Rhabdomyosarcoma Cells Cancer Res., February 1, 1999; 59(4): 886 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Law, M. E. Waltner-Law, A. J. Entingh, A. Chytil, M. E. Aakre, P. Norgaard, and H. L. Moses Salicylate-induced Growth Arrest Is Associated with Inhibition of p70s6k and Down-regulation of c-Myc, Cyclin D1, Cyclin A, and Proliferating Cell Nuclear Antigen J. Biol. Chem., December 1, 2000; 275(49): 38261 - 38267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Aoki, E. Blazek, and P. K. Vogt A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt PNAS, January 2, 2001; 98(1): 136 - 141. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
