HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 15, 10174-10181, April 14, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/15/10174    most recent M513008200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, Q. Articles by Reddy, S. P. Search for Related Content PubMed PubMed Citation Articles by Zhang, Q. Articles by Reddy, S. P. Social Bookmarking                      What's this?

A Phosphatidylinositol 3-Kinase-regulated Akt-Independent Signaling Promotes Cigarette Smoke-induced FRA-1 Expression^*

Qin Zhang, Pavan Adiseshaiah, Dhananjaya V. Kalvakolanu¹, and Sekhar P. Reddy^¶2

From the Department of Environmental Health Sciences, Bloomberg School of Public Health and ^¶Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland 21205 and University of Maryland Greenbaum Cancer Center, Baltimore, Maryland 21201

The FRA-1 proto-oncogene is overexpressed in a variety of human tumors and is known to up-regulate the expression of genes involved in tumor progression and invasion. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is also known to regulate these cellular processes. More importantly, respiratory toxicants and carcinogens activate both the PI3K-Akt pathway and FRA-1 expression in human bronchial epithelial (HBE) cells. In this study we investigated a potential link between the PI3K-Akt pathway and the cigarette smoke (CS)-stimulated epidermal growth factor receptor-mediated FRA-1 induction in non-oncogenic HBE cells. Treatment of cells with LY294002, an inhibitor of the PI3K-Akt pathway, completely blocked CS-induced FRA-1 expression. Surprisingly pharmacological inhibition of Akt had no significant effect on CS-induced FRA-1 expression. Likewise the inhibition of protein kinase C , which is a known downstream effector of PI3K, did not alter FRA-1 expression. We found that the PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by CS and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors that are bound to the promoter in HBE cells.

Received for publication, December 6, 2005 , and in revised form, January 27, 2006.

^* This work was supported in part by NIEHS, National Institutes of Health Grant ES11863 (to S. P. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by National Institutes of Health Grants CA78282 and CA105005.

² To whom correspondence should be addressed: Dept. of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Rm. E7610, 615 North Wolfe St., Baltimore, MD 21205. Tel.: 410-614-5442; Fax: 410-955-0299; E-mail: sreddy{at}jhsph.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. F. Zheng, G. J. Jones, M. Shi, J. C. D. Wiseman, K. J. Marr, B. M. Berenger, S. M. Huston, M. J. Gill, A. M. Krensky, P. Kubes, et al. Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2R{beta} That Is Defective in HIV-Infected Patients J. Immunol., June 1, 2008; 180(11): 7221 - 7229. [Abstract] [Full Text] [PDF]

				F. Yi, J. Sun, G. E. Lim, I. G. Fantus, P. L. Brubaker, and T. Jin Cross Talk between the Insulin and Wnt Signaling Pathways: Evidence from Intestinal Endocrine L Cells Endocrinology, May 1, 2008; 149(5): 2341 - 2351. [Abstract] [Full Text] [PDF]

				Y. C. Levine, G. K. Li, and T. Michel Agonist-modulated Regulation of AMP-activated Protein Kinase (AMPK) in Endothelial Cells: EVIDENCE FOR AN AMPK -> Rac1 -> Akt -> ENDOTHELIAL NITRIC-OXIDE SYNTHASE PATHWAY J. Biol. Chem., July 13, 2007; 282(28): 20351 - 20364. [Abstract] [Full Text] [PDF]

				P. Adiseshaiah, D. J. Lindner, D. V. Kalvakolanu, and S. P. Reddy FRA-1 Proto-Oncogene Induces Lung Epithelial Cell Invasion and Anchorage-Independent Growth In vitro, but Is Insufficient to Promote Tumor Growth In vivo Cancer Res., July 1, 2007; 67(13): 6204 - 6211. [Abstract] [Full Text] [PDF]

				S. Kalakonda, S. C. Nallar, D. J. Lindner, J. Hu, S. P. Reddy, and D. V. Kalvakolanu Tumor-Suppressive Activity of the Cell Death Activator GRIM-19 on a Constitutively Active Signal Transducer and Activator of Transcription 3 Cancer Res., July 1, 2007; 67(13): 6212 - 6220. [Abstract] [Full Text] [PDF]

				F. Yamasaki, M. J. Johansen, D. Zhang, S. Krishnamurthy, E. Felix, C. Bartholomeusz, R. J. Aguilar, K. Kurisu, G. B. Mills, G. N. Hortobagyi, et al. Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt Cancer Res., June 15, 2007; 67(12): 5779 - 5788. [Abstract] [Full Text] [PDF]

				P. Adiseshaiah, D. V. Kalvakolanu, and S. P. Reddy A JNK-Independent Signaling Pathway Regulates TNF{alpha}-Stimulated, c-Jun-Driven FRA-1 Protooncogene Transcription in Pulmonary Epithelial Cells J. Immunol., November 15, 2006; 177(10): 7193 - 7202. [Abstract] [Full Text] [PDF]