Disease relevance of LZTS1

• Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer [1].
• Together these data suggest that the LZTS1 gene is involved in the regulation of cell growth and its loss of function may contribute to the development of prostatic carcinomas, as well as other cancers [2].
• We have examined and found two common regions of deletion on 8p (8p12, 8p22) in oral squamous cell carcinomas (SCC)s. The possible involvement of FEZ1/LZTS1 (FEZ1) gene, a candidate tumor suppressor gene, mapped at 8p22, was also evaluated [3].
• These results add evidence supporting a role of LZTS1 in prostate cancer risk [4].
• FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells [5].

High impact information on LZTS1

• FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis [6].
• Present data show that FEZ1/LZTS1 inhibits cancer cell growth through regulation of mitosis, and that its alterations result in abnormal cell growth [6].
• The FEZ1/LZTS1 gene maps to chromosome 8p22, a region that is frequently deleted in human tumors [6].
• Alterations in FEZ1/LZTS1 expression have been observed in esophageal, breast, and prostate cancers [6].
• We found that Fez1/Lzts1 is associated with microtubule components and interacts with p34(cdc2) at late S-G(2)/M stage in vivo [6].

Biological context of LZTS1

• Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22 [2].
• Database searches also identified additional isoforms of the LZTS1 mRNA, as well as LZTS1 protein domains reminiscent of those found in transcription factors [2].
• The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors [4].
• In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls [4].
• The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors [7].

Anatomical context of LZTS1

• One possible mutation of LZTS1 (G374S) was found in a cell line [8].
• We have analysed the expression of LZTS1 in ovarian cancer and found no evidence of loss of expression relative to normal ovarian surface epithelial cells [9].
• Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases [10].

Associations of LZTS1 with chemical compounds

• Expression of FEZ1 was not restored by 5-aza-2'-deoxycytidine and trichostatin A [11].
• Unlike L1, however, FEZ-1 appeared to be monomeric in gel permeation chromatography experiments and exhibited a distinctive substrate specificity with a marked preference for cephalosporins and meropenem [12].
• The replacement of phenylalanine at 37 (F37) position with methionine caused drastical loss of IgG and IgE binding activities of human sera derived from egg allergic patients as well as disruption of the alpha-helix structure which comprises a part of the IgG and IgE epitopes [13].
• Substituting glycine at 32 position in conjunction with F37 showed a synergistic effect of decreasing antigenicity [13].
• Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a K(i) of 6.1+/-0.7muM against the FEZ-1 MBL but does not significantly inhibit the IMP-1, BcII, CphA or L1 MBLs [14].

Other interactions of LZTS1

• We report here the cloning, gene organization, cDNA sequence characterization and expression analysis of LAPSER1, an LZTS1-related gene [15].
• Hypermethylation of the CpG island flanking the Fez1/Lzts1 promoter was evident in six of the eight cell lines examined as well as in the normal control [16].

Analytical, diagnostic and therapeutic context of LZTS1

• Differential expression of FEZ1/LZTS1 gene in lung cancers and their cell cultures [11].
• To elucidate the role of FEZ1 in lung cancer, we have analyzed its expression by immunohistochemistry in 103 primary lung cancer specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32 squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small cell carcinomas [1].
• 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 [11].
• In the present study, we examined FEZ1 expression in 31 primary oral SCCs and 8 SCC-derived cell lines by reverse transcription-PCR (RT-PCR) [3].
• Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1 [17].

References