Open AccessCCAAT/enhancer binding protein‐β promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects
Author(s) -
Shimizu Yasuhito,
Kishimoto Takashi,
Ohtsuka Masayuki,
Kimura Fumio,
Shimizu Hiroaki,
Yoshidome Hiroyuki,
Miyazaki Masaru
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00596.x
Subject(s) - enhancer , cancer research , ccaat enhancer binding proteins , microbiology and biotechnology , apoptosis , chemistry , biology , medicine , biochemistry , dna binding protein , transcription factor , gene
A transcriptional factor, CCAAT/enhancer binding protein‐β (C/EBP‐β), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP‐β 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‐β 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‐β‐transfected AR42J‐B13 (βB13) 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 βB13 cells. Enhanced early survival of intraportally injected βB13 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 βB13 tumor cells than among empty vector‐transfected AR42J‐B13 (mB13) cells. Finally, intrasplenically injected βB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP‐β may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells. ( Cancer Sci 2007; 98: 1706–1713)