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Biomedical subjects

Sug Hyung Lee

Publications and source records attributed to Sug Hyung Lee.

At least 19 recordsLinked to original sources
PubMed2007

Expression of nuclear and cytoplasmic phosphorylated FADD in gastric cancers.

Fas-associated death domain (FADD) plays a crucial role during death receptor-mediated apoptosis. In addition, FADD possesses apoptosis-independent activities, including cell-cycle regulation and cell proliferation regulated by the phosphorylation of FADD at Ser194. The aim of this study was to explore the possibility whether alteration of phosphorylated FADD (p-FADD) expression might be a characteristic of gastric cancer. We analyzed the expression of p-FADD protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. In the normal gastric mucosal cells, surface and glandular epithelial cells evenly expressed p-FADD in the nuclei but not in the cytoplasm. In the cancers, p-FADD expression was detected in 38 cases (63%) of the gastric carcinomas, but there was no p-FADD immunostaining in the remaining 22 cancers (37%). Of note, p-FADD immunostaining was observed in cytoplasm/nuclei (20 cancers; 33%) and cytoplasm (18 cancers; 30%). There was no significant association of p-FADD expression with clinocopathological characteristics, including invasion, metastasis, and stage. Our data showed that the expression of p-FADD in gastric cancers was heterogenous in its location compared to the uniform nuclear expression of p-FADD in normal gastric cells. Many of the cancers (67%) were devoid of nuclear p-FADD, suggesting that p-FADD functions in the nucleus may be perturbed in the cancers. Also, p-FADD expression in the cytoplasm in a large fraction of the cancers (63%), not seen in the normal cells, suggested that the cell death functions of p-FADD could be altered in the cancer cells.

Adenocarcinoma↗
PubMed2007

Mutational analysis of PTPRT phosphatase domains in common human cancers.

A recent report revealed that the protein-tyrosine phosphatase, receptor-type, T (PTPRT) gene is somatically mutated in several types of human cancer, suggesting that the mutated PTPRT gene is a tumor suppressor gene in human cancers. However, because previously the mutational search has focused primarily on colon cancers, data on PTPRT mutations in other types of human cancer have largely been lacking. Here, we performed a mutational analysis of the PTPRT phosphatase domain by polymerase chain reaction-based single-strand conformation polymorphism (PCR-SSCP) assay in 345 cases of common human cancers, including colon carcinomas, hepatocellular carcinomas, acute leukemias, gastric carcinomas, breast carcinomas and non-small cell lung cancers. We detected PTPRT phosphatase domain mutations in 1 of 105 colon carcinomas (1%) and 1 of 48 gastric carcinomas (2%), but none in acute leukemias, hepatocellular carcinomas, breast carcinomas and non-small cell lung cancers. The PTPRT mutation detected in the colon carcinoma was a missense mutation and the mutation in the gastric carcinomas was a splice-site mutation. Contrary to the previous report on the frequent PTPTR phosphatase domain mutations in colon cancers, this study demonstrated that the somatic mutation of the PTPRT phosphatase domain rarely occurred in common human cancers. The data suggested that alterations of the PTPRT-mediated signaling pathway by PTPRT phosphatase domain mutation may not play a critical role in the development of common human cancers.

Carcinoma↗
PubMed2006

Mitochondrial microsatellite instability of colorectal cancer stroma.

Mitochondrial microsatellite instability (mtMSI) and mutations of mitochondrial DNA has been reported in cancer epithelia of carcinomas. However, mtMSI in cancer stroma has not yet been identified in human cancers. In this study, we attempted to determine if mtMSI occurs in the cancer stroma of sporadic colorectal cancers, and if the stromal mtMSI has any correlations with stromal nuclear MSI (nMSI) and cancer epithelial mtMSI. Nine microsatellite sequences within the D-loop and 5 coding genes for mtMSI, and 9 microsatellites for nMSI were analyzed in the microdissected cancer epithelia and adjacent stromas of 48 sporadic colorectal cancers. Overall, 23 somatic mitochondrial DNA alterations were detected in 15 cancer epithelia (31.2%) and 5 stromas (10.4%). The mutations consisted of 19 D-loop mtMSI alterations, and 1 missense and 3 framshift mutations of repeat sequences within the coding genes. All of the 5 stromal genetic alterations showed D-loop mtMSI. In regards to other MSI status, the stromal mtMSI had no association with stromal nMSI or epithelial mtMSI, either. These findings indicate that in addition to the cancer epithelia the cancer stroma harbor mtMSI, and suggest a possible role of stromal mtMSI in the pathogenesis of colorectal cancers. Furthermore, the data suggest that stromal mtMSI may occur independently of stromal nMSI and epithelial mtMSI in sporadic colorectal cancers.

Chromosome Mapping↗
PubMed2006

Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas.

OBJECTIVE: Mounting evidence indicates that alterations in AKT proteins play an important role in the pathogenesis of cancer. The objective of this study was to see whether common human carcinomas harbor AKT mutations that might contribute to the development of cancer. METHODS: We performed mutational analysis of the kinase domains of AKT1-AKT3 by a single-strand conformation polymorphism assay in 294 carcinoma tissues from the stomach, lung, colon and breast. RESULTS: Overall, we detected three somatic mutations in AKT2, but no mutations in AKT1 or AKT3 in the 294 cancer tissues. The AKT2 mutations were detected in 1 of 51 gastric carcinomas (2.0%) and 2 of 79 lung carcinomas (2.5%). AKT2 mutations consisted of one missense mutation and 2 splice site mutations in the intron. We simultaneously analyzed somatic mutations in EGFR, ERBB2, K-RAS, PIK3CA and BRAF genes in the 3 samples with the AKT2 mutations, and found a lung adenocarcinoma with the AKT2 missense mutation harbored an EGFR mutation. CONCLUSION: This study demonstrated that somatic mutations in the kinase domain of AKT2 occur in a small fraction of common human cancers, and suggested that alterations in the AKT2-mediated signaling pathway by AKT2 mutation could contribute to the development of some cases of human cancers.

Carcinoma↗
PubMed2006

Immunohistochemical analysis of apoptosis-inducing factor (AIF) expression in gastric carcinomas.

Mounting evidence suggests that both survival and death of cells play an important role in tumorigenesis. Apoptosis-inducing factor (AIF), a mitochondrial protein, plays an important role in the caspase-independent apoptosis. Also, recent studies have demonstrated that AIF has an oxidoreductase function that confers survival on the cells. As the roles of AIF in cancers are largely unknown, it may be important to identify the expression pattern of AIF in cancer tissues. In this study, which aims at defining the role of AIF in gastric tumorigenesis, we analyzed the expression of AIF in 60 gastric adenocarcinomas using immunohistochemistry. AIF expression was detected in the cytoplasm in 42 cases (70%) of gastric carcinoma. We also analyzed AIF expression in early (EGC) and advanced gastric carcinomas (AGC). AIF was expressed in 25 (73%) of 34 intestinal-type cancers and in 17 (65%) of 26 diffuse-type cancers. However, there was no significant difference in AIF expression with respect to the histological subtypes or the depth of invasions, either. In normal gastric mucosal cells, parietal cells, but not other mucosal cells, expressed AIF. Increased expression of AIF in malignant gastric epithelial cells compared to the normal mucosal cells suggests that AIF expression may play a role in gastric tumorigenesis. Also, the data suggest that AIF expression may play a role in the function of the gastric parietal cells.

Adenocarcinoma↗
PubMed2006

Identification of large-scale molecular changes of Autotaxin(ENPP2) knock-down by small interfering RNA in breast cancer cells.

To understand comprehensive molecular mechanisms by which Autotaxin (ENPP2) mediates, we identified large-scale molecular changes responsible for aberrant expression of Autotaxin (ATX) on breast cancer cells by using DNA microarrays. Transcriptional over-expression of ENPP2 gene was endogenously silenced by using RNA interference technique, and then recapitulated corresponding molecular changes in MDA435 breast cancer cells. Application of nonparametric Wilcoxon statistical analyses (P<0.05) and the selection criteria of 2-fold differential gene expression change resulted in the identification of 368 genes including 133 up-regulated and 235 genes under-expressed in ENPP2-silencing MDA435 cells. Most of the functional categories of identified genes are associated with cellular metabolism, cytoskeleton organization, transcription regulation, signal transduction as well as cellular organization and biogenesis. Our data suggest that the molecular signature identified by the ENPP2-silencing methods may represent potential candidates that can explain the complicated characteristics of ATX and may serve as biomarkers, for the development of molecular-targeting therapy, in human breast cancer.

Breast Neoplasms↗
PubMed2006

Somatic mutations of the ERBB4 kinase domain in human cancers.

The EGFR family consists of 4 receptor tyrosine kinases, EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Recent reports revealed that the kinase domains of both EGFR (ERBB1) and ERBB2 gene were somatically mutated in human cancers, raising the possibility that the other ERBB members possess somatic mutations in human cancers. Here, we performed mutational analysis of the ERBB4 kinase domain by polymerase chain reaction-single-strand conformation polymorphism assay in 595 cancer tissues from stomach, lung, colon and breast. We detected the ERBB4 somatic mutations in 3 of 180 gastric carcinomas (1.7%), 3 of 104 colorectal carcinomas (2.9%), 5 of 217 nonsmall cell lung cancers (2.3%) and 1 of 94 breast carcinomas (1.1%). The 12 ERBB4 mutations consisted of 1 in-frame duplication mutation and 8 missense mutations in the exons, and 3 mutations in the introns. We simultaneously analyzed the somatic mutations of EGFR, ERBB2, K-RAS, PIK3CA and BRAF genes in the 12 samples with the ERBB4 mutations and found that 1 gastric carcinoma with ERBB4 mutation also harbored K-RAS gene mutation. Our study demonstrated that in addition to EGFR and ERBB2, somatic mutation of the kinase domain of ERBB4 occurs in the common human cancers, and suggested that alterations of ERBB4-mediated signaling pathway by ERBB4 mutations may contribute to the development of human cancers.

Adult↗
PubMed2006

Mutational analysis of the kinase domain of MYLK2 gene in common human cancers.

Genetic alterations of the genes encoding protein kinases have been implicated in the development of human cancers. Myosin light chain kinase 2, skeletal muscle (MYLK2) encodes a calcium/calmodulin-dependent serine/threonine kinase. In a recent study, MYLK2 gene was somatically mutated in colorectal carcinomas. The aim of this study was to explore the possibility that other common human carcinomas besides colorectal carcinomas harbored MYLK2 mutations in the kinase domain. We analyzed exons 6 and 7 eccoding the kinase domain of MYLK2 for somatic mutations in 60 gastric, 104 colorectal, 79 non-small cell lung, and 54 breast cancers using a polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP). We found one MYLK2 mutation in lung adenocarcinomas, but not in other cancers. The MYLK2 mutation detected was a missense mutation that would substitute an amino acid (E374D) However, there was no somatic mutation of the MYLK2 gene. These data suggest that the kinase domain of MYLK2 is rarely mutated in common human carcinomas and that it does not play a dominant role in cancer pathogenesis.

Adult↗
PubMed2006

Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas.

PURPOSE: Recent reports revealed that the kinase domain of the ERBB2 gene is somatically mutated in lung adenocarcinoma, suggesting the mutated ERBB2 gene as an oncogene in human cancers. However, because previous reports focused the mutational search of ERBB2 primarily on lung cancers, the data on ERBB2 mutations in other types of human cancers have been largely unknown. EXPERIMENTAL DESIGN: Here, we did a mutational analysis of the ERBB2 kinase domain by PCR single-strand conformational polymorphism assay in gastric, colorectal, and breast carcinoma tissues. RESULTS: We detected the ERBB2 kinase domain mutations in 9 of 180 gastric carcinomas (5.0%), in 3 of 104 colorectal carcinomas (2.9%), and in 4 of 94 breast carcinomas (4.3%). All of the detected ERBB2 mutations except for one in-frame deletion mutation were missense mutations. Of the 16 ERBB2 mutations detected, 4 affected Val777 in the exon 20 site, and 3 affected Leu755 in the exon 19 site. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA, and BRAF genes in the 16 samples with ERBB2 mutations, and found that all of the 3 colorectal carcinoma samples with ERBB2 mutations harbored K-RAS mutations. CONCLUSION: This study showed that in addition to lung adenocarcinomas, ERBB2 kinase domain mutation occurs in other common human cancers such as gastric, breast, and colorectal cancers, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations alone or together with K-RAS mutations may contribute to the development of human cancers.

Aged↗
PubMed2006

BH3 domain mutation of proapoptotic genes Bad, Bmf and Bcl-G is rare in transitional cell carcinomas of the urinary bladder.

AIMS: Mounting evidence indicates that deregulation of apoptosis contributes to the development of human cancers. Bcl-2 family proteins regulate the intrinsic apoptosis pathway. The aim of this study was to explore the possibility that mutation of BH3 domain of proapoptotic Bcl-2 genes Bad, Bmf and Bcl-G might be involved in the development of urinary bladder cancer. METHODS: We analysed the BH3 domains of Bad, Bmf and Bcl-G genes for the detection of somatic mutations in 43 transitional cell carcinomas (TCCs) of the urinary bladder by a single strand conformation polymorphism assay in this study. RESULTS: There was no somatic mutation of BH3 domains of Bad, Bmf and Bcl-G genes in the TCC samples. CONCLUSION: The data presented here indicate that BH3 domain mutation of these genes is rare in TCCs and may not contribute to the pathogenesis of TCCs.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas.

AIMS: Evasion of apoptosis is one of the hallmarks of cancer. Bax-interacting factor-1 (Bif-1) interacts with both Bax and Bak that are essential for the intrinsic pathway of apoptosis, and enhances apoptosis. The aim of this study was to explore whether alteration of Bif-1 expression might be a characteristic of gastric cancer. METHODS: We analysed the expression of Bif-1 protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. RESULTS: In normal gastric mucosal cells, surface and glandular epithelial cells strongly expressed Bif-1. While Bif-1 expression was detected in 24 cases (40%) of the gastric carcinomas, there was no Bif-1 immunostaining in the remaining 36 cancers. Even in the 24 cases with positive Bif-1 immunostainings, 10 cancers showed decreased intensity of immunostaining compared with the normal mucosal epithelial cells. CONCLUSION: The decreased expression of Bif-1 in malignant gastric epithelial cells compared with the normal mucosal cells suggests that loss of Bif-1 expression may play a role in gastric tumorigenesis, possibly by inhibiting the apoptosis mediated by Bif-1.

Adaptor Proteins, Signal Transducing↗