Age Factors ; Bone Neoplasms ; secondary ; Breast Neoplasms ; chemistry ; genetics ; pathology ; Carcinoma, Ductal, Breast ; chemistry ; genetics ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; genetics ; pathology ; Female ; Gene Expression Profiling ; Humans ; Ki-67 Antigen ; analysis ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; analysis ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Tumor Burden

OBJECTIVETo observe the effect of Tiam-l gene silencing on the metastasis of human colorectal carcinoma cell line SW480 in nude mice by real-time whole-body fluorescence imaging.

METHODSEnhanced green fluorescence protein (EGFP)-labeled human colorectal carcinoma cells, SW480/EGFP(+)/Tiam-1(-) and SW480/EGFP(+), were implanted into nude mice via tail vein injection or orthotopic colonal inoculation, and real-time whole-body fluorescence imaging was performed to compare the difference in tumor progression and metastasis between the two cells.

RESULTSBoth SW480/EGFP(+) and SW480/ EGFP(+)/Tiam-1(-) cells stably expressed EGFP, and Tiam1 gene expression was reduced in SW480/EGFP(+)Tiam-1(-) to 30% of the expression level in SW480/EGFP(+) cells. The growth rate of the two cell lines had no significant difference in vitro (P>0.05), but SW480/EGFP(+)/Tiam1(-) cell proliferation and metastasis were depressed obviously in comparison with SW480/EGFP(+) in vivo (P<0.05).

CONCLUSIONTiam-1 gene may play an important role in invasion and metastasis of human colorectal cancer.

Animals ; Blotting, Western ; Bone Neoplasms ; genetics ; metabolism ; secondary ; Cell Line, Tumor ; Cell Survival ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Diagnostic Imaging ; methods ; Female ; Fluorescence ; Gene Silencing ; Green Fluorescent Proteins ; chemistry ; genetics ; metabolism ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Transplantation ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transplantation, Heterologous

Expressions of p53 protein, a product of the tumor suppressor gene were studied in osteosarcomas relating to various prognostic factors. Thirty-four osteosarcomas were investigated immunohistochemically with a monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins and another clone PAb1801, which reacts with both wild- and mutant-type p53 proteins. The results were compared with expressions of proliferating cell nuclear antigen (PCNA) and Ki-67 providing a simple method for the assessment of growth fractions of tumors. PAb240 stained nuclei and cytoplasm of tumor cells in 8 of 34 osteosarcomas (23.5%), whereas PAb1801 reacted in all 34 osteosarcomas (100%). Fifteen tumors (44.1%) showed positivity for PAb1801 in more than half of the tumor cells. Twelve patients were alive and thirteen were dead. Tumors from 9 patients (75%) who survived revealed only focal positive immunoreactions with PAb1801 and tumors from 6 patients (46.1%) who died revealed diffuse reactions. Twelve cases (35.3%) showed a high PCNA index (> 40%) and fibroblastic osteosarcomas revealed the highest PCNA positivity. Twenty-two cases (64.7%) revealed a very low Ki-67 index (less than 10%) and Ki-67 index showed a good correlation with PCNA positivity (r = 0.6247). Expressions of both wild-and mutant-type p53 protein, PCNA, and Ki-67 were not correlated with other clinical or pathological parameters.
Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; Bone Neoplasms/*chemistry/genetics/pathology ; Cell Cycle/physiology ; Child ; Child, Preschool ; Genes, p53 ; Human ; Immunohistochemistry ; Ki-67 Antigen ; Male ; Middle Age ; Mutation ; Neoplasm Proteins/*analysis ; Nuclear Proteins/*analysis ; Osteosarcoma/*chemistry/genetics/pathology ; Proliferating Cell Nuclear Antigen/*analysis ; Protein p53/*analysis ; Support, Non-U.S. Gov't