Expression of the Fanconi anemia gene FAC in human cell lines: lack of effect of oxygen tension.
Fanconi anemia (FA) is a recessively inherited disease characterized by bone marrow failure, congenital anomalies, chromosomal instability and hypersensitivity to crosslinking agents. Some of the cellular defects of FA are known to be responsive to the ambient oxygen concentration. We examined the responsiveness of the FA complementation group C (FAC) gene to changes in oxygen concentration using two types of human cell lines, hypoxia-responsive Hep3B hepatoma cells and Epstein-Barr virus-immortalized lymphoblasts (normal and FA complementation groups B and C). Although the expression of erythropoietin in Hep3B cells was induced in response to the hypoxia-mimicking agent CoCl₂, there was no concomitant induction in FAC expression as assessed by mRNA levels and immunoprecipitable protein, and no detectable change in the cytoplasmic location of the FAC polypeptide as determined by indirect immunofluorescence. In human lymphoblasts we examined the effect of oxygen (0.1% -95% O₂) on cell proliferation and FAC expression. FA lymphoblasts had a normal sensitivity to the cytostatic effect of hyperoxia, while in both control and FA lymphoblasts FAC mRNA levels were unaffected by oxygen. Our results indicate that ambient oxygen is not a regulator of the FAC gene.
Joenje
H
H
Department of Human Genetics, Free University, Amsterdam, The Netherlands.
Youssoufian
H
H
Kruyt
F A
FA
dos Santos
C C
CC
Wevrick
R
R
Buchwald
M
M
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D018797:Cell Cycle Proteins; D015687:Cell Hypoxia; D002461:Cell Line, Transformed / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004921:Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D004854:Herpesvirus 4, Human; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins; D010100:Oxygen / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D004921:Erythropoietin; D003035:Cobalt; C018021:cobaltous chloride; D010100:Oxygen