Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration

Background T-lymphoma and metastasis gene 1 （Tiaml） produces a guanine nucleotide exchange factor （GNEF） that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiaml was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiara1 in gastric carcinoma. Methods We analyzed the expression of Tiaml in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiaml expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiaml over-expression were analyzed with stable-expression Tiara1 plasmid in human gastric cancer cell lines. Results Tiaml expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiaml mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiaml expression had significantly shorter overall survival time than those with negative Tiaml expression. Ectopic expression of Tiaml promoted cell growth, migration and invasion of gastric cancer cells in vitro. Conclusions In gastric cancer cells, Tiaml affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer

Aim: To identify the metastasis suppressor genes for prostate cancer. Methods: A copy of human chromosomeswas introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediatedchromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clonesand the number of lung metastases produced by the clones were analyzed to determine which part of human chromo-somes contained the metastasis suppressor gene (s) for prostate cancer. To determine portions of human chromosomesintroduced, G-banding chromosomal analysis, fluorescence in sim hybridization analysis, and polymerase chain reac-tion analysis were performed. Results: Each of microcell hybrid clones containing human chromosomes 7, 8, 10,11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstratesthat these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portionsof human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromo-some 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletionsof human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasissuppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2,12p11-q13, 12q24-ter, and 17pter-q23. KAII and MKK4/SEKI were identified as metastasis suppressor genes from11p11. 2 and 17p12, respectively. Conclusion: This assay system is useful to identify metastasis suppressor gene(s) for prostate cancer.

RELATIONSHIP BETWEEN THE MUTATION OF P53 GENE AND INFILTRATION，METASTASIS AND PROGNOSIS OF GASTRIC CARCINOMA

gastric carcinomas were examined immunohistochemically with McAb to p53 protein in order to investigate the relationship between the expression of p53 protein and histological differentiation of gastric carcinoma, and to approach the mechanism of infiltration and metastasis of gastric carcinoma. The results showed that nuclear expression of p53 protein was significantly related to tumor size, depth of invasion, lymph node and liver metastases; but not related to histological differentiation. It is suggested that the accumulation of p53 protein was increased with the progression of gastric carcinoma, and therefore the cancer clone with p53 gene mutation may play an important role in the development of tumor invasion and metastasis.

KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate cancer in Chinese

Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 withCaP (adenocarcinoma clinical stage C and D) were analyzed by means of immunohistochemical methods. Results:The KAII/CD82 expression in BPH tissue was all positive, which was uniformly located on the glandular cell mem-brane at the cell-to-cell borders, but KAII/CD82 expression in metastasis CaP tissues was either significantly lower thanthat of BPH or negative, and the immunostaining pattern was not continuous. In late-stage CAP KAII/CD82 expressionwas correlated inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P > 0.05). Conclusion:The authors believe that decreased and negative KAII/CD82 expression in late-stage CaP may be related to tumor pro-gression and metastasis, and appears to be a prognostic marker.

IDENTIFICATION OF A NEW HUMAN nm23 GENE,nm23-H3b

Nm23 is a kind of effective tumor metastasis suppressor genes which included two types in human:nm23-H1 and nm23-H2. Amino acid identity between nm23-H1 and nm23-H2 was 88%.In this study,using a pair of primers to flank the part of coding sequence of nm 23,the 5'-translated sequence was amplified by polymerase chain reaction (PCR) from human normal liver genomic DNA.A 375-base pairs clone was charactertzed,which designated pnm23-H3b.The nm23-H3b nucleotide sequence between 40 bp and 70 bp is different from nm23-H1 and nm23-H2,and other sequences have 86%and 90%identical to nm23-H1 and nm23-H2,respectively.Southern blot containing BglⅡ-digested human liver genomic DNA hybridized to the entire nm23-H3b DNA and showed three bands at 10.5,7.9 and 4.0 Kb.These data demonstrate that the third human nm23 exists possibly.Therefore,nm23 may be considered a family of closely related genes.

Positive association of RhoC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma

Worldwide estimates establish gastric carcinoma as the second most frequent cause of cancer deaths. Tumour invasion and metastasis is the biggest impediment to gastric carcinoma cure. Active migration of tumour cells is now considered as the pivotal step in cancer invasion and metastasis. RhoC is a member of the Ras-superfamily of small guanosine triphosphatases that can regulate many cellular functions, especially cytoskeletal organization and cell locomotion. Overexpressing RhoC in vitro in the poorly metastatic cell line from human melanoma may induce a highly metastatic phenotype.~1 The recent development of laser capture microdissection (LCM) affords the opportunity to further evaluate the role RhoC plays in the invasion and metastasis of gastric carcinoma cells in their native tissue environment.