CCAAT/enhancer binding protein-beta promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects.
A transcriptional factor, CCAAT/enhancer binding protein-beta (C/EBP-beta), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP-beta in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP-beta in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J-B13, as this step profoundly affects metastatic efficiency. C/EBP-beta-transfected AR42J-B13 (betaB13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl-2 and Bcl-xL was seen in betaB13 cells. Enhanced early survival of intraportally injected betaB13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector-specific gene, was observed. Nick-end labeling analysis of the tumor-injected liver revealed significantly lower rates of apoptosis among intravascular betaB13 tumor cells than among empty vector-transfected AR42J-B13 (mB13) cells. Finally, intrasplenically injected betaB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP-beta may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells.
Shimizu
Yasuhito
Y
Departments of Molecular Pathology, and General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Kishimoto
Takashi
T
Ohtsuka
Masayuki
M
Kimura
Fumio
F
Shimizu
Hiroaki
H
Yoshidome
Hiroyuki
H
Miyazaki
Masaru
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology*; D051381:Rats; D014183:Transplantation, Heterologous
D022782:CCAAT-Enhancer-Binding Protein-beta