Cancer Research Cancer Epigenetics Genetics and Biology of Brain Cancer
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
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clark, A. S.
Right arrow Articles by Dennis, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clark, A. S.
Right arrow Articles by Dennis, P. A.
[Cancer Research 63, 780-786, February 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Altered Protein Kinase C (PKC) Isoforms in Non-Small Cell Lung Cancer Cells

PKC{delta} Promotes Cellular Survival and Chemotherapeutic Resistance

Amy S. Clark, Kip A. West, Peter M. Blumberg and Phillip A. Dennis1

Cancer Therapeutics Branch [A. S. C., K. A. W., P. A. D.] and Laboratory of Cellular Carcinogenesis and Tumor Promotion [P. M. B.], Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889

Drugs that target protein kinase C (PKC) are now being evaluated in patients with non-small cell lung cancer (NSCLC), but the role of PKC in NSCLC cells remains unclear. We report here that NSCLC cell lines show enhanced phosphorylation and altered expression of specific PKC isoforms compared with normal lung epithelial cells. PKC inhibition variably increased apoptosis, with rottlerin, a PKC{delta} inhibitor, being most effective and potentiating chemotherapy-induced apoptosis, especially with trastuzumab. Consistent with PKC{delta} being anti-apoptotic in NSCLC cells, transient transfection of a kinase-dead mutant of PKC{delta} increased apoptosis and potentiated chemotherapy-induced apoptosis. Our studies provide a rationale for targeting PKC isoforms in NSCLC cells, especially PKC{delta}.




This article has been cited by other articles:


Home page
 Eur Respir JHome page
H. Slevogt, L. Maqami, K. Vardarowa, W. Beermann, A. C. Hocke, J. Eitel, B. Schmeck, A. Weimann, B. Opitz, S. Hippenstiel, et al.
Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms
Eur. Respir. J., April 1, 2008; 31(4): 725 - 735.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
Y. Oh, R. S. Herbst, H. Burris, A. Cleverly, L. Musib, M. Lahn, and G. Bepler
Enzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non-Small-Cell Lung Cancer
J. Clin. Oncol., March 1, 2008; 26(7): 1135 - 1141.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
P. Shivshankar, L. Lei, J. Wang, and G. Zhong
Rottlerin Inhibits Chlamydial Intracellular Growth and Blocks Chlamydial Acquisition of Sphingolipids from Host Cells
Appl. Envir. Microbiol., February 15, 2008; 74(4): 1243 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J.-A. Park, A. L. Crews, W. R. Lampe, S. Fang, J. Park, and K. B. Adler
Protein Kinase C{delta} Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein
Am. J. Pathol., December 1, 2007; 171(6): 1822 - 1830.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Chen, C. Gould, R. Garza, T. Gao, R. Y. Hampton, and A. C. Newton
Amplitude Control of Protein Kinase C by RINCK, a Novel E3 Ubiquitin Ligase
J. Biol. Chem., November 16, 2007; 282(46): 33776 - 33787.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
T. Uekita, L. Jia, M. Narisawa-Saito, J. Yokota, T. Kiyono, and R. Sakai
CUB Domain-Containing Protein 1 Is a Novel Regulator of Anoikis Resistance in Lung Adenocarcinoma
Mol. Cell. Biol., November 1, 2007; 27(21): 7649 - 7660.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. S. Herbst, Y. Oh, A. Wagle, and M. Lahn
Enzastaurin, a Protein Kinase C{beta} Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4641s - 4646s.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K.-M. Bae, H. Wang, G. Jiang, M. G. Chen, L. Lu, and L. Xiao
Protein Kinase C{varepsilon} Is Overexpressed in Primary Human Non-Small Cell Lung Cancers and Functionally Required for Proliferation of Non-Small Cell Lung Cancer Cells in a p21/Cip1-Dependent Manner
Cancer Res., July 1, 2007; 67(13): 6053 - 6063.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
R. Gomel, C. Xiang, S. Finniss, H. K. Lee, W. Lu, H. Okhrimenko, and C. Brodie
The Localization of Protein Kinase C{delta} in Different Subcellular Sites Affects Its Proapoptotic and Antiapoptotic Functions and the Activation of Distinct Downstream Signaling Pathways
Mol. Cancer Res., June 1, 2007; 5(6): 627 - 639.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Xia, L. W. Forman, and D. V. Faller
Protein Kinase C{delta} Is Required for Survival of Cells Expressing Activated p21RAS
J. Biol. Chem., May 4, 2007; 282(18): 13199 - 13210.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
L Sabater, L Bataller, A F Carpentier, M L Aguirre-Cruz, A Saiz, B Benyahia, J Dalmau, and F Graus
Protein kinase C{gamma} autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer
J. Neurol. Neurosurg. Psychiatry, December 1, 2006; 77(12): 1359 - 1362.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. A. Teicher
Protein kinase C as a therapeutic target.
Clin. Cancer Res., September 15, 2006; 12(18): 5336 - 5345.
[Full Text] [PDF]

Home page
 JCOHome page
M. A. Carducci, L. Musib, M. S. Kies, R. Pili, M. Truong, J. R. Brahmer, P. Cole, R. Sullivan, J. Riddle, J. Schmidt, et al.
Phase I Dose Escalation and Pharmacokinetic Study of Enzastaurin, an Oral Protein Kinase C Beta Inhibitor, in Patients With Advanced Cancer
J. Clin. Oncol., September 1, 2006; 24(25): 4092 - 4099.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. H. Choi, T. Hyman, and P. M. Blumberg
Differential Effect of Bryostatin 1 and Phorbol 12-Myristate 13-Acetate on HOP-92 Cell Proliferation Is Mediated by Down-regulation of Protein Kinase C{delta}.
Cancer Res., July 15, 2006; 66(14): 7261 - 7269.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. Paz-Ares, J.-Y. Douillard, P. Koralewski, C. Manegold, E. F. Smit, J. M. Reyes, G.-C. Chang, W. J. John, P. M. Peterson, C. K. Obasaju, et al.
Phase III Study of Gemcitabine and Cisplatin With or Without Aprinocarsen, a Protein Kinase C-Alpha Antisense Oligonucleotide, in Patients With Advanced-Stage Non-Small-Cell Lung Cancer
J. Clin. Oncol., March 20, 2006; 24(9): 1428 - 1434.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Nakagawa, J. L. Oliva, D. Kothapalli, A. Fournier, R. K. Assoian, and M. G. Kazanietz
Phorbol Ester-induced G1 Phase Arrest Selectively Mediated by Protein Kinase C{delta}-dependent Induction of p21
J. Biol. Chem., October 7, 2005; 280(40): 33926 - 33934.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. E. Santiago-Walker, A. J. Fikaris, G. D. Kao, E. J. Brown, M. G. Kazanietz, and J. L. Meinkoth
Protein Kinase C {delta} Stimulates Apoptosis by Initiating G1 Phase Cell Cycle Progression and S Phase Arrest
J. Biol. Chem., September 16, 2005; 280(37): 32107 - 32114.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q. Pan, L. W. Bao, C. G. Kleer, M. S. Sabel, K. A. Griffith, T. N. Teknos, and S. D. Merajver
Protein Kinase C{varepsilon} Is a Predictive Biomarker of Aggressive Breast Cancer and a Validated Target for RNA Interference Anticancer Therapy
Cancer Res., September 15, 2005; 65(18): 8366 - 8371.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Mohanty, J. Huang, and A. Basu
Enhancement of Cisplatin Sensitivity of Cisplatin-Resistant Human Cervical Carcinoma Cells by Bryostatin 1
Clin. Cancer Res., September 15, 2005; 11(18): 6730 - 6737.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Hurbin, J.-L. Coll, L. Dubrez-Daloz, B. Mari, P. Auberger, C. Brambilla, and M.-C. Favrot
Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells
J. Biol. Chem., May 20, 2005; 280(20): 19757 - 19767.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. Wiedlocha, T. Nilsen, J. Wesche, V. Sorensen, J. Malecki, E. Marcinkowska, and S. Olsnes
Phosphorylation-regulated Nucleocytoplasmic Trafficking of Internalized Fibroblast Growth Factor-1
Mol. Biol. Cell, February 1, 2005; 16(2): 794 - 810.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
O. David, J. Jett, H. LeBeau, G. Dy, J. Hughes, M. Friedman, and A. R. Brody
Phospho-Akt Overexpression in Non-Small Cell Lung Cancer Confers Significant Stage-Independent Survival Disadvantage
Clin. Cancer Res., October 15, 2004; 10(20): 6865 - 6871.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. A. Villalona-Calero, P. Ritch, J. A. Figueroa, G. A. Otterson, R. Belt, E. Dow, S. George, J. Leonardo, S. McCachren, G. L. Miller, et al.
A Phase I/II Study of LY900003, an Antisense Inhibitor of Protein Kinase C-{alpha}, in Combination with Cisplatin and Gemcitabine in Patients with Advanced Non-Small Cell Lung Cancer
Clin. Cancer Res., September 15, 2004; 10(18): 6086 - 6093.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. B. Deb, C. M. Coticchia, and R. B. Dickson
Calmodulin-mediated Activation of Akt Regulates Survival of c-Myc-overexpressing Mouse Mammary Carcinoma Cells
J. Biol. Chem., September 10, 2004; 279(37): 38903 - 38911.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
D. N. JACKSON and D. A. FOSTER
The enigmatic protein kinase C{delta}: complex roles in cell proliferation and survival
FASEB J, April 1, 2004; 18(6): 627 - 636.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Q. Wang, X. Wang, and B. M. Evers
Induction of cIAP-2 in Human Colon Cancer Cells through PKC{delta}/NF-{kappa}B
J. Biol. Chem., December 19, 2003; 278(51): 51091 - 51099.
[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
Copyright © 2003 by the American Association for Cancer Research.