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 Toyooka, S. Articles by Gazdar, A. F. Search for Related Content PubMed PubMed Citation Articles by Toyooka, S. Articles by Gazdar, A. F.

Differential Expression of FEZ1/LZTS1 Gene in Lung Cancers and Their Cell Cultures¹

Hamon Center for Therapeutic Oncology Research [S. T., Y. F., J. D. M., A. F. G.], and Departments of Pathology [A. F. G.], Internal Medicine [J. D. M.], and Pharmacology [J. D. M.], University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593; Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile [I. I. W.]; and Molecular Screening Laboratory, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612-9497 [M. S. T.]

Purpose: The FEZ1/LZTS1 (FEZ1) gene, located on chromosome 8p22 (8p22), was identified recently as a candidate tumor suppressor gene. Because loss of heterozygosity at 8p21–22 is a frequent event in lung cancers, we studied FEZ1 alteration in short-term cultures of resected lung cancer tumors and cell lines.

Experimental Design: We examined FEZ1 expression in 17 non-small cell lung cancer (NSCLC), 19 small cell lung cancer (SCLC) cell lines, and 6 pairs of short-term cultures of resected NSCLCs and accompanying nonmalignant bronchial cells (NBECs) by reverse transcription-PCR and Western blotting. To investigate the mechanism for silencing, cells were cultured with 5-aza-2'-deoxycytidine or trichostatin A. We screened for genomic mutations by PCR-single-strand conformational polymorphism.

Results: Thirteen of 17 NSCLC (76%) and 3 of 19 SCLC (16%) of cell lines showed absent expression (P = 0.001). Of the paired NSCLC-NBEC cultures, 3 of 6 showed loss of expression in tumor cell cultures. In the cell lines retaining expression, the amplicon products in SCLCs were more intense than those of NSCLCs and NBECs. Expression of FEZ1 was not restored by 5-aza-2'-deoxycytidine and trichostatin A. Although FEZ1 expression was moderately correlated with loss of heterozygosity of specific microsatellite makers at 8p21–22 in NSCLC cell lines, it was strongly correlated to D8S261 and LPL loci in SCLC cell lines. No mutation was found within cording region of FEZ1 by PCR-single-strand conformational polymorphism.

Conclusions: We found differential FEZ1 expression in NSCLC and SCLC cell lines, and the absent expression in 3 of 6 short-term cultures of NSCLC tumors. FEZ1 may be related to tumorigenesis of lung cancer.

This article has been cited by other articles:

				R. Baffa, M. Fassan, C. Sevignani, A. Vecchione, H. Ishii, E. Giarnieri, R. V. Iozzo, L. G. Gomella, and C. M. Croce Fez1/Lzts1-deficient mice are more susceptible to N-butyl-N-(4-hydroxybutil) nitrosamine (BBN) carcinogenesis Carcinogenesis, April 1, 2008; 29(4): 846 - 848. [Abstract] [Full Text] [PDF]

				G. Thyssen, T.-H. Li, L. Lehmann, M. Zhuo, M. Sharma, and Z. Sun LZTS2 Is a Novel {beta}-Catenin-Interacting Protein and Regulates the Nuclear Export of {beta}-Catenin Mol. Cell. Biol., December 1, 2006; 26(23): 8857 - 8867. [Abstract] [Full Text] [PDF]

				D. Nonaka, A. Fabbri, L. Roz, L. Mariani, A. Vecchione, G. W. Moore, L. Tavecchio, C. M. Croce, and G. Sozzi Reduced FEZ1/LZTS1 Expression and Outcome Prediction in Lung Cancer Cancer Res., February 15, 2005; 65(4): 1207 - 1212. [Abstract] [Full Text] [PDF]

				S. Toyooka, K. O. Toyooka, K. Miyajima, J. L. Reddy, M. Toyota, U. G. Sathyanarayana, A. Padar, M. S. Tockman, S. Lam, N. Shivapurkar, et al. Epigenetic Down-Regulation of Death-associated Protein Kinase in Lung Cancers Clin. Cancer Res., August 1, 2003; 9(8): 3034 - 3041. [Abstract] [Full Text] [PDF]