Downregulation of the coxsackie and adenovirus receptor in cancer cells by hypoxia depends on HIF-1alpha.
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Downregulation of the coxsackie and adenovirus receptor in cancer cells by hypoxia depends on HIF-1alpha. / Küster, K; Koschel, A; Rohwer, N; Fischer, A; Wiedenmann, B; Anders, Mario.
In: CANCER GENE THER, Vol. 17, No. 2, 2, 2010, p. 141-146.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Downregulation of the coxsackie and adenovirus receptor in cancer cells by hypoxia depends on HIF-1alpha.
AU - Küster, K
AU - Koschel, A
AU - Rohwer, N
AU - Fischer, A
AU - Wiedenmann, B
AU - Anders, Mario
PY - 2010
Y1 - 2010
N2 - Loss of the coxsackie and adenovirus receptor (CAR) has been found in various human cancers. Underlying mechanisms, however, are still poorly understood. Therefore, the objective of this study was to investigate the function of hypoxia, a ubiquitous phenomenon in carcinomas, in CAR regulation. In our approach, hypoxia and treatment with cobalt-(II)-chloride (CoCl(2)) induced a downregulation of CAR protein and mRNA expression, as well as a suppression of CAR gene promoter activity in AGS (gastric), SW480 (colon) and PC3 (prostate) cancer cells. In line with these findings we noted a decreased adenoviral uptake under hypoxic conditions. Aiming to further elucidate the molecular basis of this observation, a full-length hypoxia-inducible factor-1alpha (HIF-1alpha) cDNA was ectopically overexpressed in the AGS cell line diminishing CAR expression and CAR gene promoter activity. In line with these findings, exposure of HIF-1alpha-deficient AGS cells to hypoxia did not alter CAR mRNA expression level. On the basis of these data, it may be suggested that loss of CAR in human cancer cell lines under hypoxic conditions occurs in an HIF-1alpha-dependent manner.
AB - Loss of the coxsackie and adenovirus receptor (CAR) has been found in various human cancers. Underlying mechanisms, however, are still poorly understood. Therefore, the objective of this study was to investigate the function of hypoxia, a ubiquitous phenomenon in carcinomas, in CAR regulation. In our approach, hypoxia and treatment with cobalt-(II)-chloride (CoCl(2)) induced a downregulation of CAR protein and mRNA expression, as well as a suppression of CAR gene promoter activity in AGS (gastric), SW480 (colon) and PC3 (prostate) cancer cells. In line with these findings we noted a decreased adenoviral uptake under hypoxic conditions. Aiming to further elucidate the molecular basis of this observation, a full-length hypoxia-inducible factor-1alpha (HIF-1alpha) cDNA was ectopically overexpressed in the AGS cell line diminishing CAR expression and CAR gene promoter activity. In line with these findings, exposure of HIF-1alpha-deficient AGS cells to hypoxia did not alter CAR mRNA expression level. On the basis of these data, it may be suggested that loss of CAR in human cancer cell lines under hypoxic conditions occurs in an HIF-1alpha-dependent manner.
M3 - SCORING: Zeitschriftenaufsatz
VL - 17
SP - 141
EP - 146
JO - CANCER GENE THER
JF - CANCER GENE THER
SN - 0929-1903
IS - 2
M1 - 2
ER -
