OBJECTIVETo investigate the expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) in breast carcinomas, and explore its association with the clinicopathological features of breast carcinoma.

METHODSImmunohistochemistry was used to detect Tiam1 expression in normal breast tissue and 126 breast carcinoma tissues, and the expression levels of Tiam1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting, respectively.

RESULTSThe expression of Tiam1 was significantly higher in breast carcinomas than in normal breast tissue (P<0.05). Tiam1 expression was not correlated to the age of the patients or the histological type (P>0.05), but to lymph node metastasis and clinical stages of the tumor (P<0.01). Tiam1 mRNA and protein expressions were stronger in breast carcinoma cell line MDA-MB-435 with high metastatic potential than in breast carcinoma cell line MCF-7.

CONCLUSIONTiam1 is closely related to the metastasis of breast carcinoma, and may play an important role in promoting metastasis of breast carcinoma.

Adult ; Aged ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo investigate the relationship between the protein expression of T-lymphoma invasion and metastasis gene 1 (Tiam-1) and the biological behaviors of nasopharyngeal carcinoma (NPC).

METHODSImmunohistochemistry was performed to detect the expressions of Tiam-1 protein in 60 specimens of NPC tissue, 20 specimens of chronic nasopharyngitis (CN) tissue, and 6 tumor tissues from nude mice inoculated with metastatic human NPC cells.

RESULTSThe positivity rate and average score for Tiam-1 expression were significantly higher in NPC tissues than in CN tissue (63.33% vs 36.67%, 2.9167 +/- 1.3057 vs 0.7000 +/- 0.9234; chi(2)=20.429, P=0.001; t=7.0162, P=0.0000, respectively). No difference was found in Tiam-1 expression among NPC patients in different T stages (F=2.36, P=0.0811), while the expression differed significantly between the patients with lymph node metastasis and those without metastasis, and also between patients with organ metastasis and those without (P=0.0001). High Tiam-1 expressions were found in the tumor tissues in nude mice inoculated with metastatic NPC cells.

CONCLUSIONTiam-1 expression is closely associated with the invasiveness and metastasis of NPC, indicating that Tiam-1 is an important factor that promotes the invasion and metastasis of NPC.

Adult ; Aged ; Animals ; Female ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Humans ; Male ; Mice ; Mice, Nude ; Middle Aged ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo investigate the relationship between the expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) and the progression, metastasis, TNM stage, and histological types of lung carcinoma.

METHODSImmunohistochemistry was performed to detect the expression of Tiam1 in 116 lung carcinoma specimens. The expression intensity (measured in positive unit, PU) of Tiam1 in these tissues was assessed quantitatively using Imagepro Plus image analysis software.

RESULTSThe PU of Tiam1 was significantly greater in primary lung carcinomas with lymph node metastases than in those without metastases (t=-2.089, P=0.039). Lung cancers of TNM stage II-IV had stronger expression than those of stage I (t=-2.272, P=0.025). The PU of Tiam1 differed significantly between different histological types of lung cancer, and squamouscell cell carcinoma had a lower PU than adenocarcinoma, large cell carcinoma and small cell carcinoma (P<0.05). The intensity of Tiam1 expression was not associated with the patients' gender, age, general types, smoking history, pneumoconiosis or differentiation of lung carcinoma.

CONCLUSIONThese results strongly suggest that Tiam1 is an invasion and metastasis inducing factor of lung carcinoma. The overexpression of Tiam1 is closely associated with lymph node metastases, TNM stage and histological types of lung carcinoma.

Adenocarcinoma ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Guanine Nucleotide Exchange Factors ; metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

BACKGROUNDT-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma.

METHODSWe analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines.

RESULTSTiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 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 Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro.

CONCLUSIONSIn gastric cancer cells, Tiam1 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.

Cell Line, Tumor ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Humans ; Neoplasm Metastasis ; genetics ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo investigate whether the Tiam1 gene expression enhances the invasive and metastatic capabilities of colorectal carcinoma cells.

METHODSEndogenous expression of Tiam1 in five colorectal carcinoma cell lines was investigated by RT-PCR. Tiam1/C1199HA cDNA was transfected into HT29, a colorectal carcinoma cell line without endogenous Tiam1 expression. RNA and protein expression of Tiam1 gene in the transfectants were detected by RT-PCR, immunohistochemistry and Western blot respectively. The biological behaviors of the transfectants were investigated by MTT and in-vitro invasion assays.

RESULTSTiam1 gene was highly expressed in LoVo and SW620 cells. Low level expression was seen in HCT116 and SW480 and no expression was found in HT29. Transfection of Tiam1 significantly increased the proliferation of HT29 cells along with markedly enhanced in-vitro invasion and metastasis.

CONCLUSIONSTiam1 gene plays an important role in the invasion and metastasis of colorectal carcinoma. It may be a useful marker for metastasis of colorectal carcinoma.

Biomarkers, Tumor ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; physiology ; HT29 Cells ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transfection

Adult ; Aged ; Aged, 80 and over ; Female ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Humans ; Keratin-18 ; genetics ; metabolism ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo explore biological aspects of Tiam1 gene expression in nasopharyngeal carcinoma cells.

METHODSTiam1/C1199HA expression plasmids were transfected into nasopharyngeal carcinoma cells of C666-1 and CNE1 by lipofectamine2000. RT-PCR, real-time PCR and Western blot Analyses were performed to evaluate the expression of Tiam1 mRNA and protein levels, respectively. In vitro cell adhesion, wound healing and matrigel invasion assays were used to study the biological impact of Tiam1 on cell adhesion, mobility and invasion.

RESULTSTiam1 over expression significantly increased the abilities of adhesion, migratory and invasion of C666-1 and CNE1 cells, comparing with that of the control untransfected cells (P < 0.05).

CONCLUSIONTiam1 expression correlates with the invasion and metastasis of nasopharyngeal carcinoma cells.

Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; physiology ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Plasmids ; RNA, Messenger ; metabolism ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo investigate the effects of T lymphoma invasion and metastasis inducing factor 1 antisense oligodeoxynucleotides (Tiam 1 ASODN) transfection on the morphology and invasive migration potential of gastric cancer cells.

METHODSThe higher invasive and migratory subgroup (M(H)) were separated from human gastric cancer cell line MKN-45 (M(0)) by laminin adhesion method in vitro. Tiam 1 ASODN was transfected into M(H) cells with liposome, and the expression of Tiam 1 mRNA and protein was determined by RT-PCR and flowcytometry respectively. The changes in morphology, the invasive and migratory potential between Tima 1 ASODN transfected M(H) cells and no transfected M(H) cells were observed by HE stain, cytoskeletal protein stain, scanning electronic microscope (SEM) and Boyden chamber test.

RESULTSCompared with the control, the expression of Tiam 1 mRNA and protein in M(H) cells was significantly decreased after transfected with 0.43 micromol/L ASODN(P< 0.01). The invasive and migratory potential of M(H) cells in vitro was also much more decreased than that of no transfected cells (P< 0.05 or P< 0.01). At the same time, transfected M(H) cells had less membrane surface projections, fewer or shorter pseudopodia, less irregular cytoskeletal network and less spotted-like actin bodys than no transfected M(H) cells did.

CONCLUSIONTiam 1 ASODN transfection can effectively suppress the expression of Tiam 1 in gastric cancer cells and impair its invasive and migratory potential in vitro, which may be fulfilled through modulating the reconstruction of cytoskeleton and decreasing the deforming and migratory potential of gastric cancer cells.

Animals ; Cell Line, Tumor ; Flow Cytometry ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; Oligonucleotides, Antisense ; genetics ; RNA, Messenger ; genetics ; Stomach Neoplasms ; genetics ; pathology ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transfection

OBJECTIVETo investigate the association of single nucleotide polymorphisms (SNP) rs22833188 and rs2833195 in TIAM1 gene with the susceptibility to Kawasaki disease (KD) and its clinical characteristic in children.

METHODSA case-control study was performed in this study. One hundred and eighty-eight children with KD and 197 normal children served as controls were enrolled. The genotypes of two SNPs rs22833188 and rs2833195 in TIAM1 gene were detected using PCR-RFLP.

RESULTSThere were no significant differences in the genotype (AA, AG and GG) and allele frequencies of SNP rs2833188 between the KD and control groups. Significant differences in the genotype (CC, GC and GG) frequency of SNP rs2833195 were noted between the KD and control groups (P=0.017). The frequency of C allele in the KD group was higher than in the control group (P=0.015). The polymorphism of SNP rs2833188 was associated with the occurrence of rash (P=0.011), and the polymorphism of SNP rs2833195 was associated with the occurrence of conjunctival hyperemia (P=0.021).

CONCLUSIONSThe polymorphism of rs2833195 in TIAM1 gene is associated with the susceptibility to KD. The polymorphisms rs2833188 and rs2833195 in TIAM1 gene may be associated with some clinical characteristics in children with KD.

Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVE: To investigate the effect of T lymphoma invasion and metastasis 1 (Tiam 1) overexpression in head and neck squamous cell carcinoma (HNSCC) cells. METHOD: Endogenous expression of Tiam 1 in 8 head and neck squamous cell carcinoma cell (HNSCC) lines was investigated by real-time RT-PCR. A lentivirus vector containing Tiaml was transfected into UM-SCC-47 cells, a head and neck squamous cell carcinoma cell line with little endogenous Tiaml expression. Stable clone, obtained by G418 screening, were assayed by RT-PCR and Western blot to validate the gene expression efficiency. The biological behaviors of the transduced cells were determined by cell counting, MTT and in-vitro migration assay. RESULT: Tiam 1 gene was highly expressed in M2 cell line and it's low level expression was found in UM-SCC-47. Cell counting and MTT assay showed that over-expression of Tiaml significantly promoted cell proliferation (P < 0.05). The cell monolayers overexpressed Tiaml that resulted in a significant increasment of cell migration in infected head and neck squamous cell carcinoma cell lines (P < 0.05). CONCLUSION Tiam 1 gene plays an important role in the growth and migration in head and neck squamous cell carcinoma cell lines. It may be a useful marker for metastasis of head and neck squamous cell carcinoma.
Blotting, Western ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Squamous Cell Carcinoma of Head and Neck ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transfection