Relevance of apoptosis and tolerance to hypoxic stress in cells transfected with receptor for advanced glycation end products (RAGE).
BACKGROUND
It has previously been reported that RAGE plays a role in resisting hypoxia in cancer cells. Here the mechanism of resistance of RAGE-transfected Cos7 cells to hypoxia is investigated from the standpoint of apoptosis.


METHODS
RAGE-transfected and mock-transfected Cos7 cells were subjected to hypoxia for 12, 24 and 36 h in an MTT assay. The expression of the apoptosis-regulatory proteins, hypoxia inducible factor-1(HIF-1a) and p53 in them was assessed by Western blotting.


RESULTS
RAGE-transfected Cos7 cells showed better survival than mock-transfected Cos7 cells during hypoxia. The expression of many apoptosis-regulatory proteins was not affected. However, the expression of HIF-1a and p53 was weaker in RAGE-transfected Cos7 cells than in mock-transfected Cos7 cells.


CONCLUSIONS
The presence of RAGE might suppress HIF-1a protein expression, which in turn might induce an anti-apoptosis effect in RAGE-transfected Cos7 cells. Moreover, the p53 suppression induced by HIF-1a may lead to malignant potential in RAGE-transfected Cos7 cells.
Departments of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima 890-8520, Japan.
Kiyokazu
K
Hiwatashi
Shinichi
S
Ueno
Fumitake
F
Kubo
Masahiko
M
Sakoda
Taro
T
Tateno
Tomomi
T
Hayashi
Kazuhiro
K
Abeyama
Shoji
S
Natsugoe
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D019556:COS Cells / Q000378:metabolism; D002522:Chlorocebus aethiops; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000067759:Receptor for Advanced Glycation End Products; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein