Biomedical subjects

Jian-Tao Cui

Publications and source records attributed to Jian-Tao Cui.

4 recordsLinked to original sources

PubMed2004

Antisense targeting protein kinase C alpha and beta1 inhibits gastric carcinogenesis.

Protein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCalpha, PKCbeta1, and PKCbeta2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCalpha-AS and PKCbeta1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCalpha-AS and PKCbeta1-AS transfectants. PKCalpha-AS and PKCbeta1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCbeta2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCalpha and PKCbeta1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCalpha or PKCbeta1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCalpha or PKCbeta1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCalpha and PKCbeta1 by antisense method is a promising therapy for gastric cancer.

Animals↗

PubMed2004

Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage.

Ataxia telangiectasia mutated (ATM) is the gene mutated in the genetic disorder ataxia telangiectasia (AT), the symptoms of which include sensitivity to radiation and an increased risk of cancer. ATM is a kinase involved in activating the appropriate damage-response pathway, leading to either cell-cycle arrest or apoptosis, and is therefore a key checkpoint molecule in regulating cell-cycle response to DNA damage and responsible for maintenance of genome integrity. However, little is known about the association of ATM mutations with human gastric cancer (HGC). In order to determine the mutation and mRNA expression changes of the ATM gene in HGC, we performed analyses by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and RT-PCR technique on 13 human gastric tumor cell lines and 30 cases of fresh tumor specimens matched normal tissue. We compared the potential effect of the ATM gene mutation and cell behavior including cell-cycle arrest and induction of apoptosis in the tumor cell lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure. Our data show that frequent variations were observed at 10 exons and 2 cDNA fragments which covered 8 other exons of the ATM gene as 5 out of 13 on the cell lines (38.5%) and 2 out of 30 cases in the tissue specimens (6.7%). All point mutations were confirmed as base substitutions (5982T-C; 6620A-G; 8684G-G/A; 9389C-G) and deletions (1079delC) by use of DNA sequencing. Among the mutations, one was reported previously in breast cancer, the other five have not yet been reported. The expression of ATM was significantly lower in five cell lines (MGC803; MKN45; SGC7901; GES and SUN-1) than in two others (BGC823 and RF48). G2/M cell-cycle arrest and apoptosis were observed in ATM-deficient MGC803 cells challenged with IR. A transient up-regulation of p53 occurred 1h post-IR in BGC823 cells but not in MGC803 cells. Our findings suggest that ATM mutations might be a pathogenic factor for an increased risk of gastric cancer, and the dysfunction of ATM may lead to a hypersensitivity to ionizing radiation in gastric cancer cells, possibly by a p53-dependent pathway.

Ataxia Telangiectasia Mutated Proteins↗

PubMed2003

[Mutations of fragile histidine triad gene in Peutz-Jeghers syndrome and canceration].

BACKGROUND & OBJECTIVE: Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. Fragile histidine triad (FHIT) gene is an important tumor suppressor gene at the fragile sites region of 3p14. The authors' previous study suggested that PJS patients might have a susceptible gene at the region of 3p14.2. This study was designed to reveal the relationship between the variant of FHIT gene in PJS and its canceration. METHOD: Mutations of FHIT gene in 15 PJS patients and 20 unaffected members in 6 PJS families were determined using denaturing high-performance liquid chromatography (DHPLC), polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and DNA sequencing techniques. RESULTS: A non-sense mutation and a frame-shift mutation were identified at codon 54(GAA to TAA) (exon 6) which led to the change of the amino acid from glutamic acid (Glu) to stop codon, and a guanine insertion at codon 62 in exon 6 resulting in a premature stop codon TGA at codon 111 in one PJS patient. A homozygous deletion and a synonymous mutation were detected in exon 8. The homozygous deletion of exon 8 in FHIT gene was found in two polyps tissues and two cancerous tissues. And in 3 sporadic cases, the patients and their mothers have the same bands of SSCP and the same elution profiles of DHPLC when exon 8 was amplified. The DNA sequencing result showed that a synonymous mutation (polymorphism) occurred at codon 98 [CAT (H)-->CAC (H)], this mutation resulted in no change of amino acid. In addition, one base substitute from A to G mutation at 5'end, +42 nucleotide in intron 6 of FHIT gene was detected in seven patients and two unaffected members. CONCLUSION: PJS patients have low frequency point mutation of FHIT gene and their cancerous tissues had homozygous deletions in FHIT gene. This study indicated that the mutations and deletions of FHIT gene in PJS may play a role in the development of PJS and their cancerations.

Acid Anhydride Hydrolases↗

PubMed2002

Construction of cDNA representational difference analysis based on two cDNA libraries and identification of garlic inducible expression genes in human gastric cancer cells.

AIM: To elucidate molecular mechanism of chemopreventive efficacies of garlic against human gastric cancer (HGC). METHODS: HGC cell line BGC823 was treated with Allitridi (a kind of garlic extract) and Allitridi-treated and parental BGC823 cDNA libraries were constructed respectively by using lambdaZAP II vector. cDNA Representational Difference Analysis (cDNA RDA) was performed using Bam H I cutting-site and abundant cDNA messages provided by the libraries. Northern blot analysis was applied to identify the obtained difference products. RESULTS: Two specific cDNA fragments were obtained and characterized to be derived from homo sapiens folate receptor alpha (FRalpha) gene and calcyclin gene respectively. Northern blot results showed a 4-fold increase in FRalpha gene expression level and 9-fold increase in calcyclin mRNA level in BGC823 cells after Allitridi treatment for 72h. CONCLUSION: The method of cDNA RDA based on cDNA libraries combines the high specificity of cDNA RDA with abundant cDNA messages in cDNA library; this expands the application of cDNA library and increases the specificity of cDNA RDA. Up-regulation of FRalpha gene and calcyclin gene expressions induced by Allitridi provide valuable molecular evidence for the efficacy garlic in treating HGC as well as other diseases.

Allyl Compounds↗