Biomedical subjects

Jaehwi Song

Publications and source records attributed to Jaehwi Song.

6 recordsLinked to original sources

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

Genetic and epigenetic alterations of the KLF6 gene in hepatocellular carcinoma.

BACKGROUND AND AIM: Kruppel-like factor 6 (KLF6) is a zinc finger tumor suppressor gene that is frequently mutated in several human cancers and is broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. The aim of this study was to elucidate the potential etiological role of KLF6 in the development of hepatocellular carcinoma (HCC) in Korea. METHODS: The gene mutation, allelic loss, and methylation status of the KLF6 gene was analyzed in a series of 85 Korean patients: 21 with dysplastic nodules and 85 with HCC. RESULTS: No somatic mutations were observed in the patients with dysplastic nodules or with HCC. Allelic loss was found in five (6.8%) of 73 informative HCC tissues. Three of the five patients with allelic loss had HCC with hepatitis B virus infection and cirrhosis, and the remaining two had no viral infection and a non-specific background. In methylation analysis, unmethylated and methylated DNAs of the KLF6 gene were amplified in all corresponding non-neoplastic liver tissues. Only one HCC tissue showed methylated DNA without unmethylated DNA. CONCLUSIONS: The results suggest that genetic and epigenetic alteration of KLF6 may play a minor role in the development of HCC.

Adult↗

PubMed2005

Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate.

Autotaxin (ATX) was originally identified as a potent tumor cell motility-stimulating factor that displays multiple enzymatic activities including ATPase, Type I nucleotide pyrophosphatase/phosphodiesterase, and lysophospholipase D, depending on its substrates. We demonstrate herein that ATX is a key regulator of extracellular lysophosphatidic acid (LPA) that can act as survival factor, in addition to its mitogenic activity in mouse fibroblasts. Introduction of atx gene into NIH3T3 cells resulted in resistance to conditional apoptosis induced by serum-deprivation, and exogenous ATX protein prevented cells from death by starvation. Flow cytometric analysis showed that co-treatment of ATX with lysophosphatidylcholine as substrate rescued NIH3T3 cells from cellular apoptosis, and this survival activity of ATX was also demonstrated by caspase-3 degradation and PARP cleavage resulting from the enzymatic activity of extracellular ATX. Furthermore, the effect of ATX in preventing apoptosis appears to be mediated through the G-protein-coupled receptor pathway followed by the activation of phosphoinositide 3-kinase and Akt pathway leading to enhanced cell survival. These findings provide novel insights into understanding the functions of ATX as a key regulator of bioactive phospholipids and suggest interventions to correct dysfunction in conditions of tumor cell growth and metastasis.

Animals↗

PubMed2005

Increased expression of histone deacetylase 2 is found in human gastric cancer.

Accumulated evidence has established that aberrant regulation of histone deacetylases (HDACs) is one of the major causes of the development of human malignancies. Among different iso-enzymes of HDAC and sirtuins grouped as the HDAC super family, little is known as to how histone deacetylase 2 (HDAC2) causes carcinogenesis in solid tumors. Here, in order to investigate the possible role of HDAC2 in gastric carcinogenesis, we analyzed the expression of HDAC2 in 71 gastric adenocarcinomas by immunohistochemistry. Moderate to strong expression of HDAC2 was found in 44 (62%) out of a total of 71 tumors. The majority of positive tumors, which were detected in the nucleus but not in normal gastric epithelium, did not express HDAC2 or showed only weak positive staining. Interestingly, we also noted that HDAC2 expression appeared to be associated with tumor aggressiveness as HDAC2 expression was observed to be statistically significant in advanced gastric cancer (P=0.0023, Chi-square test) and in positive lymph node metastasis (P=0.0713, Chi-square test). Taken together, these results suggest that HDAC2 may play an important role in the aggressiveness of gastric cancer.

Adenocarcinoma↗

PubMed2004

Application of amplified RNA and evaluation of cRNA targets for spotted-oligonucleotide microarray.

Among different RNA amplification methods, T7 RNA polymerase-based in vitro transcription (IVT) that generates antisense RNA is most common in DNA microarray protocol. However, despite the fact that cRNA targets labeled during IVT are feasible for spotted-oligonucleotide microarray (spotted-oligoarray) hybridization due to complementary sequence of single-stranded oligonucleotide probe, no systemic assessment for the use of amplified cRNA targets has been reported for spotted-oligoarrays. In this investigation, we have compared the hybridization performance of amplified cRNA targets with that of cDNA targets from total RNA(T-RNA) using spotted-oligoarrays containing 18,864 genetic elements. Under the optimized hybridization conditions, we found that 86% of oligonucleotide probes were reproducibly detected by both cDNA and cRNA target protocols. In addition, cRNA targets generated by two-rounds of amplification of 10 ng T-RNA were concordant with first-round cRNA targets generated from 100 ng T-RNA by 0.858 of correlation coefficient. Taken together, we demonstrated that cRNA targets from very scant RNA amount could successfully be applied on spotted-oligoarrays, and hopefully this will facilitate the application of much smaller amount of source material based on the high-fidelity and improved target preparation of microarrays.

Gene Targeting↗

PubMed2004

Different gene expression profiles between microsatellite instability-high and microsatellite stable colorectal carcinomas.

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability (CIN) and microsatellite instability (MSI), exist in colorectal carcinomas. In order to clarify the molecular signature related to the CIN and MSI in colorectal carcinomas, we performed transcriptomic expression analysis on eight microsatellite instability-high (MSI-H) colorectal carcinomas and compared the results obtained with that of nine microsatellite stable (MSS) colorectal carcinomas using oligonucleotide microarrays containing 17 334 known genes and 1331 unknown genes or expression sequence tags (ESTs). Unsupervised two-way hierarchical clustering with 5724 genes successfully classified tumors from normal mucosa, and displayed a distinctive MSI-H carcinomas subgroup. Based on intensive filtering, 57 known genes and eight ESTs were found to be highly relevant to the differentiation of MSI-H and MSS colorectal carcinomas. These genes successfully distinguish the new test set of six MSI-H and five MSS colorectal carcinomas. Many up- and downregulated genes in MSI-H colorectal carcinomas were related to the previously reported phenotypic characteristics; increased mucin production and intense peritumoral immune response in MSI-H carcinomas. Some of these differences were confirmed by semiquantitative reverse transcription-PCR and immunohistochemical analysis. Our findings indicate that there are many different genetic and transcriptomic characteristics between MSI-H and MSS colorectal carcinomas, and some of these differently expressed genes can be used as diagnostic or prognostic markers.

Base Sequence↗