Metallothionein IIA is up-regulated by hypoxia in human A431 squamous carcinoma cells.
The expression of metallothionein IIA (MT-IIA) was investigated in A431 human squamous carcinoma cells exposed to hypoxia (pO < or = 0.01% of atmospheric pO2) and subsequent reoxygenation. Northern analysis showed that MT-IIA mRNA levels were significantly increased during 14 h of hypoxia and during reoxygenation. Western blotting confirmed that total MT protein levels were also increased in response to these stresses. Evidence of the transcriptional control of MT-IIA expression in hypoxic and in reoxygenated A431 cells was found using a 0.2-kilobase sequence of the proximal 5'-regulatory region of the MT-IIA gene in a chloramphenicol acetyltransferase reporter gene construct. Thus the proximal promoter of the human MT-IIA gene appears to contain a hypoxic response element(s). These observations indicate that MT-IIA may have an important role in the stress responses of cells in solid tumors.
Murphy
B J
BJ
Cell and Molecular Biology Laboratory, SRI International, Menlo Park, California 94025.
Laderoute
K R
KR
Chin
R J
RJ
Sutherland
R M
RM
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C050087:oxygen-regulated proteins; D008668:Metallothionein; D015500:Chloramphenicol O-Acetyltransferase