Enhanced S100A4 protein expression is clinicopathologically significant to metastatic potential and p53 dysfunction in colorectal cancer.
To investigate the expression levels of S100A4 in human colorectal carcinoma (CC) and its relationship with clinicopathological parameters and metastatic potential, 73 pathological specimens from patients with CC were examined for S100A4 expression by RT-PCR and immunohistochemistry. An increase of S100A4 mRNA was observed in 19/23 (82.6%) CC specimens, and S100A4 was up-regulated in 40/73 (54.7%) CC cases compared with non-neoplastic mucosal tissues. Upregulation of S100A4 was significantly related to invasion, nodal status, distant metastasis and p53 expression. Next, we investigated whether S100A4 could affect p53 transactivation and stability. Interestingly, it was revealed that treatment with exogenous S100A4 protein reduced transcriptional activity of p53 and abrogated the modification of calcium binding affinity of S100A4 protein. These findings suggested that S100A4 might be involved in the progression and metastasis of human CC, presumably via modulation of the wild-type p53 protein.
Kim
Joo Heon
JH
Department of Pathology, Eulji University School of Medicine, Daejeon, Korea.
Kim
Chang Nam
CN
Kim
Soo Young
SY
Lee
Jung Sam
JS
Cho
Daeho
D
Kim
Jae Wha
JW
Yoon
Sun Young
SY
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D055550:Protein Stability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C077591:S100A4 protein, human; D002118:Calcium