Activated Raf-1 causes growth arrest in human small cell lung cancer cells

The Journal of Clinical Investigation
R K RaviM Mabry

Abstract

Small cell lung cancer (SCLC) accounts for 25% of all lung cancers, and is almost uniformly fatal. Unlike other lung cancers, ras mutations have not been reported in SCLC, suggesting that activation of ras-associated signal transduction pathways such as the raf-MEK mitogen-activated protein kinases (MAPK) are associated with biological consequences that are unique from other cancers. The biological effects of raf activation in small cell lung cancer cells was determined by transfecting NCI-H209 or NCI-H510 SCLC cells with a gene encoding a fusion protein consisting of an oncogenic form of human Raf-1 and the hormone binding domain of the estrogen receptor (DeltaRaf-1:ER), which can be activated with estradiol. DeltaRaf-1:ER activation resulted in phosphorylation of MAPK. Activation of this pathway caused a dramatic loss of soft agar cloning ability, suppression of growth capacity, associated with cell accumulation in G1 and G2, and S phase depletion. Raf activation in these SCLC cells was accompanied by a marked induction of the cyclin-dependent kinase (cdk) inhibitor p27(kip1), and a decrease in cdk2 protein kinase activities. Each of these events can be inhibited by pretreatment with the MEK inhibitor PD098059. These data dem...Continue Reading

References

Oct 27, 1989·Science·T TakahashiJ D Minna
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·T Hirakawa, H E Ruley
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·T NakagawaS B Baylin
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 9, 1995·Nature·D O Morgan
Nov 18, 1994·Cell·R W KingM W Kirschner
Jul 1, 1994·Trends in Biochemical Sciences·J AvruchJ M Kyriakis
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·I E SchauerR A Sclafani
Mar 1, 1994·Cancer Metastasis Reviews·N G Williams, T M Roberts
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K W WoodS Halegoua
Dec 1, 1995·Molecular Reproduction and Development·M Marshall
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·K M Pumiglia, S J Decker

❮ Previous
Next ❯

Citations

Mar 4, 2000·Journal of Cellular Physiology·A SgambatoI B Weinstein
Nov 30, 2011·Endocrine·Krystallenia I Alexandraki, Gregory Kaltsas
Mar 21, 2003·Biochemical and Biophysical Research Communications·Renu WadhwaSunil C Kaul
Feb 26, 2000·Progress in Histochemistry and Cytochemistry·T Ito
May 5, 2001·Pharmacology & Therapeutics·C R Weinstein-OppenheimerJ A McCubrey
May 9, 2001·Biochimica Et Biophysica Acta·M McMahon, D Woods
Dec 7, 2011·Cell Research·Jihan K OsborneMelanie H Cobb
Oct 7, 2009·The Journal of Biological Chemistry·Seung-Keun HongJong-In Park
Jul 21, 2005·Thyroid : Official Journal of the American Thyroid Association·Herbert ChenJamie J Van Gompel
Feb 21, 2006·Thyroid : Official Journal of the American Thyroid Association·Barbara J CollinsXiulong Xu
Jan 24, 2006·Anti-cancer Drugs·Muthusamy Kunnimalaiyaan, Herbert Chen
Jan 14, 2010·Journal of Oncology·Scott N PinchotHerbert Chen
Jun 4, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yafei LiPing Yang
Apr 1, 1999·American Journal of Respiratory Cell and Molecular Biology·R K RaviM Mabry
Apr 1, 1999·American Journal of Respiratory Cell and Molecular Biology·S J Weintraub
Jul 24, 2012·BMC Complementary and Alternative Medicine·Abdalrahim F A AishaAmin Malik Shah Abdul Majid
Apr 23, 2009·Cell Communication and Signaling : CCS·Gerald ThielOliver G Rössler
Aug 27, 2009·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Michael LeeKi-Hwan Eum
Jul 8, 2014·Frontiers in Biology·Jong-In Park
Mar 16, 2006·Apoptosis : an International Journal on Programmed Cell Death·S CagnolJ-C Chambard
Mar 17, 2010·Journal of the Chinese Medical Association : JCMA·Kam-Tsun Tang, Chen-Hsen Lee
Nov 26, 2010·Endocrinology and Metabolism Clinics of North America·Barbara Zarebczan, Herbert Chen
Jan 8, 2004·The Journal of Investigative Dermatology·Niina HietaVeli-Matti Kähäri
Apr 15, 2008·Biochemical and Biophysical Research Communications·Thomas W Sturgill
Jul 21, 2011·Molecular Systems Biology·Adam L CohenAndrea H Bild
Jul 29, 2010·Journal of Cellular Physiology·Olga BermudezClotilde Gimond
Feb 7, 2014·Journal of Cellular Physiology·Jean-Philippe GuéganGeorges Baffet
Aug 13, 2013·Gene·A A StepanenkoV M Kavsan
Aug 2, 2007·Expert Opinion on Therapeutic Targets·Efstathia PapageorgiouMichael Koutsilieris
Feb 27, 1999·Experimental Cell Research·M R SmithS M Rybak
Sep 2, 2006·Biochemical and Biophysical Research Communications·Hyo Jung KimHan Geuk Seo
Nov 28, 2006·Biochimica Et Biophysica Acta·James A McCubreyRichard A Franklin
Jan 6, 2010·Carcinogenesis·Théodora S Niault, Manuela Baccarini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.