Differential expression of FEZ1/LZTS1 gene in lung cancers and their cell cultures.
OBJECTIVE
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.


METHODS
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.
Toyooka
Shinichi
S
Hamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
Fukuyama
Yasuro
Y
Wistuba
Ignacio I
II
Tockman
Melvyn S
MS
Minna
John D
JD
Gazdar
Adi F
AF
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C528597:FEZ1 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C118711:LZTS1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine