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Metallothionein IIA Is Up-Regulated by Hypoxia in Human A431 Squamous Carcinoma Cells¹

Cell and Molecular Biology Laboratory, SRI International, Menlo Park, California 94025

The expression of metallothionein IIA (MT-IIA) was investigated in A431 human squamous carcinoma cells exposed to hypoxia (pO₂ 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.

¹ This study was supported by NIH Grants CA57692 (B. J. M.) and CA20329 (R. M. S.).

² To whom requests for reprints should be addressed, at SRI International, Room LA257, 333 Ravenswood Avenue, Menlo Park, CA 94025.

Received 7/15/94. Accepted 10/ 6/94.

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