This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Chiosea, S. Articles by Dacic, S. Search for Related Content PubMed PubMed Citation Articles by Chiosea, S. Articles by Dacic, S.

Overexpression of Dicer in Precursor Lesions of Lung Adenocarcinoma

¹ Department of Pathology, University of Pittsburgh Medical Center; ² Department of Pharmacology, University of Pittsburgh School of Medicine; ³ University of Pittsburgh Cancer Institute, Hillman Cancer Center; and ⁴ Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania

Requests for reprints: Simion Chiosea, Department of Pathology, University of Pittsburgh Medical Center Presbyterian, C920, 200 Lothrop Street, Pittsburgh, PA 15213. Phone: 412-958-5459; Fax: 412-624-0614; E-mail: chioseasi{at}upmc.edu.

Differential microRNA (miR) expression is described in non–small cell lung carcinoma. miR biogenesis requires a set of proteins collectively referred to as the miR machinery. In the proposed multistep carcinogenesis model, peripheral adenocarcinoma of the lung develops from noninvasive precursor lesions known as atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). The gene array analysis of BAC and adenocarcinoma showed a transient up-regulation of Dicer (a key effector protein for small interfering RNA and miR function) and PACT along with down-regulation of most genes encoding miR machinery proteins. Immunohistochemically, Dicer was up-regulated in AAH and BAC and down-regulated in areas of invasion and in advanced adenocarcinoma. A fraction of adenocarcinomas lose Dicer as a result of deletions at the Dicer locus. Expanded immunohistochemical and Western blot analysis showed higher Dicer level in squamous cell carcinoma (SCC) of the lung when compared with adenocarcinoma. Other proteins of the RNA-induced silencing complex (RISC; SND1, PACT, and FXR1) were also present at higher levels in a SCC cell line when compared with an adenocarcinoma cell line. In conclusion, the stoichiometry of miR machinery and RISC depends on histologic subtype of lung carcinoma, varies along the AAH-BAC-adenocarcinoma sequence, and might explain the observed abnormal miR profile in lung cancer. The status of the endogenous miR machinery in various histologic subtypes and stages of lung cancer may help to predict the toxicity of and susceptibility to future RNA interference–based therapy. [Cancer Res 2007;67(5):2345–50]

This article has been cited by other articles:

				O. Kovalchuk, J. Filkowski, J. Meservy, Y. Ilnytskyy, V. P. Tryndyak, V. F. Chekhun, and I. P. Pogribny Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin Mol. Cancer Ther., July 1, 2008; 7(7): 2152 - 2159. [Abstract] [Full Text] [PDF]

				M. E. Armstrong, M. Gantier, L. Li, W. Y. Chung, A. McCann, J. A. Baugh, and S. C. Donnelly Small Interfering RNAs Induce Macrophage Migration Inhibitory Factor Production and Proliferation in Breast Cancer Cells via a Double-Stranded RNA-Dependent Protein Kinase-Dependent Mechanism J. Immunol., June 1, 2008; 180(11): 7125 - 7133. [Abstract] [Full Text] [PDF]

				L. Zhang, S. Volinia, T. Bonome, G. A. Calin, J. Greshock, N. Yang, C.-G. Liu, A. Giannakakis, P. Alexiou, K. Hasegawa, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer PNAS, May 13, 2008; 105(19): 7004 - 7009. [Abstract] [Full Text] [PDF]

				H. Yang, C. P. Dinney, Y. Ye, Y. Zhu, H. B. Grossman, and X. Wu Evaluation of Genetic Variants in MicroRNA-Related Genes and Risk of Bladder Cancer Cancer Res., April 1, 2008; 68(7): 2530 - 2537. [Abstract] [Full Text] [PDF]