The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors

Abstract

Alterations of human chromosome 8p occur frequently in many tumors. We identified a 1.5-Mb common region of allelic loss on 8p22 by allelotype analysis. cDNA selection allowed isolation of several genes, including FEZ1. The predicted Fez1 protein contained a leucine-zipper region with similarity to the DNA-binding domain of the cAMPresponsive activating-transcription factor 5. RNA blot analysis revealed that FEZ1 gene expression was undetectable in more than 60% of epithelial tumors. Mutations were found in primary esophageal cancers and in a prostate cancer cell line. Transcript analysis from several FEZ1-expressing tumors revealed truncated mRNAs, including a frameshift. Alteration and inactivation of the FEZ1 gene may play a role in various human tumors.

Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

“…The latter cell line has been shown by Northern blot analysis not to express the full length LZTS1 mRNA (Ishii et al, 1999). The results of these experiments are shown in Figure 5a.…”

“…Based on the published pattern of expression and the function (when known) of these genes, all except LZTS1 were excluded from further study as potential TSGs. Even though the function of the LZTS1 gene is unknown, it was previously identi®ed as a candidate TSG on the basis of its di erential expression in tumor and normal tissues in several types of cancers (Ishii et al, 1999). It was isolated originally from a YAC (859A7) that overlaps with YACs 911G7 and 739B2.…”

“…However, when the endogenous LZTS1 expression in these cell lines was checked by RT ± PCR the levels of expression of this gene in both cell lines were comparable; in fact, the only noticeable di erence between these cell lines appeared to be in the expression of the minor isoforms observed in the TSUPr1 cells, as shown in Figure 5b. (Figure 2a) led to the identi®cation of the LZTS1 gene, previously known as FEZ1 (Ishii et al, 1999), as potentially responsible for the observed growth inhibitory e ects of these clones on AT6.2 cell. Ectopic expression of LZTS1 cDNA in AT6.2 cells resulted in inhibition of colony-forming e ciency and a signi®cantly decreased growth rate.…”

“…Positional cloning methods have led to the isolation of at least three genes localized to 8p21-22, PDGFRL (also known as PRLTS; Fujiwara et al, 1995), NKX3.1 (Bhatia-Gaur et al, 1999) and N33 , that have been postulated as candidate cancer genes. More recently, another gene from 8p22, referred to as FEZ1 (F37/Esophageal cancer-related genecoding leucine-zipper motif), has been isolated and found to be altered in several tumors including esophageal, breast and prostate (Ishii et al, 1999). The HUGO Human Gene Nomenclature committee has now designated this locus as the LZTS1 (leucine zipper, putative tumor suppressor 1) gene.…”

HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

“…Therefore, 8p might harbor one or more tumorsuppressor genes that are important in progression, especially the metastasis of cancers, including HCC (Nihei et al, 2002). Several candidate tumor-suppressor genes have been identified from 8p, including DLC-1 (8p21.3-22) (Yuan et al, 1998), FEZ1 (8p22) (Ishii et al, 1999), liverrelated putative tumor suppressor gene (8p23) (Liao et al, 2000), PCM1 (which encodes a centrosomal protein), and DUSP4/MKP-2 (which encodes a MAP kinase phosphatase) (Armes et al, 2004). However, alterations in these genes may occur as an early event in the development of cancers, and their association with metastasis has not been confirmed (Park et al, 2002), even though one very recent study indicated that FEZ1 may serve as a novel prognostic indicator for lung cancer (Nonaka et al, 2005).…”