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DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells. The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics. DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months). Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels. Cancer 2002;95:2473–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10987

Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome and the fidelity of sister chromatid separation. Failure of such checkpoint functions results in genomic instability, a condition that predisposes cells to neoplastic transformation and tumor progression. Recently, Scolnick and Halazonetis defined a new mitotic checkpoint that acts at prophase and delays chromosome condensation in response to mitotic stress, and identified a gene, named checkpoint with FHA and ring finger (Chfr), that seems to be required for delaying prophase in human cells. In the present study, we examined human Chfr mRNA expression in 15 human esophageal cancer cell lines and 43 primary esophageal cancers to investigate the potential involvement of Chfr in the pathogenesis of esophageal cancers. We report here that a significant proportion of human esophageal cancer has loss of expression of Chfr gene. Furthermore, we found aberrant hypermethylation of the promoter region of this checkpoint gene in four of 15 (26.7%) esophageal cancer cell lines and in seven of 43 (16.3%) primary cancers.

Members of the Rho family of small guanosine triphosphatases (Rho-GTPases) have emerged as key coordinators of signaling pathways leading to remodeling of the actin cytoskeleton, a process that plays a critical role in cell adhesion and migration. However, the precise regulatory mechanisms remain to be elucidated. Here we report isolation of a novel human gene, ARHGAP9, which encodes a protein containing a Rho-GTPase activating protein (Rho-GAP) domain, a src-homology 3 (SH3) domain, a pleckstrin homology (PH) region, and a WW domain. In vitro, the recombinant protein revealed substantial GAP activity toward Cdc42Hs and Rac1, and less toward RhoA. The transcript was predominantly expressed in peripheral blood leukocytes, spleen, and thymus. Exogenous expression of the entire coding region of ARHGAP9 into human leukemia KG-1 cells repressed adhesion of the cells to fibronectin and collagen IV. Our results indicate that ARHGAP9 is involved in regulating adhesion of hematopoietic cells to extracellular matrix.

β‐Catenin, a key regulator of cellular proliferation, is often mutated in various types of human cancer. To investigate cellular responses related to the β‐catenin signaling pathway, we applied a differential display method using mouse cells transfected with an activated form of mutant β‐catenin. This analysis and subsequent northern‐blot hybridization confirmed that expression of a murine gene encoding NBL4 (novel band 4.1‐like protein 4) was up‐regulated by activation of β‐catenin. To examine a possible role of NBL4 in cancer, we isolated the human homologue of the murine NBL4gene by matching mNBL4against the human EST (expressed sequence tag) database followed by 5’ rapid amplification of cDNA ends (5′RACE). The cDNA of hNBL4encoded a protein of 598 amino acids that shared 87% identity in amino acid sequence with murine NBL4 and 71% with zebrafish NBL4. A 2.2‐kb hNBL4 transcript was expressed in all human tissues examined with high levels of expression in brain, liver, thymus and peripheral blood leukocytes and low levels of expression in heart, kidney, testis and colon. We determined its chromosomal localization at 5q22 by fluorescence in situhybridization. Expression of hNBL4was significantly reduced when β‐catenin was depleted in SW480 cells, a human cancer cell line that constitutionally accumulates β‐catenin. The results support the view that NBL4 is an important component of the β‐catenin/Tcf pathway and is probably related to determination of cell polarity or proliferation.