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Downregulation of metallothionein-IIA expression occurs at immortalization

Oncogene volume 18, pages 897–903 (1999)Cite this article

Abstract

Metallothioneins (MTs) may modulate a variety of cellular processes by regulating the activity of zinc-binding proteins. These proteins have been implicated in cell growth regulation, and their expression is abnormal in some tumors. In particular, MT-IIA is expressed 27-fold less in human colorectal tumors and tumor cell lines compared with normal tissue (Zhang et al., 1997). Here we demonstrate that MT-IIA downregulation occurs when human cells become immortal, a key event in tumorigenesis. After immortalization MT-IIA expression remains inducible but the basal activity of the MT-IIA promoter is decreased. MT-IIA downregulation at immortalization is one of the most common immortalization-related changes identified to date, suggesting that MT-IIA has a role in this process.

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Acknowledgements

We thank Dr Adrian West for providing oligonucleotide probe sequences and plasmids, Kilian Perrem for technical assistance, and Lindy Hodgkin for help with the manuscript. This study was supported by an Australian Postgraduate Award (to ED) and the New South Wales Cancer Council Carcinogenesis Fellowship (to RR).

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  1. Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, 2145, NSW, Australia

    Emma L Duncan & Roger R Reddel

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Duncan, E., Reddel, R. Downregulation of metallothionein-IIA expression occurs at immortalization. Oncogene 18, 897–903 (1999). https://doi.org/10.1038/sj.onc.1202370

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