The two faces of metallothionein in carcinogenesis: photoprotection against UVR-induced cancer and promotion of tumour survival

Abstract

Metallothionein is a multi-functional protein that protects the host against toxic heavy metals. Under stressful situations it can protect against oxidative damage, contribute to tissue repair, modulate immune responses and limit inflammatory processes. Recently, metallothionein's role in ultraviolet radiation (UVR)-induced injury has been investigated. These studies have shown that when metallothionein is upregulated following exposure to UVR, it can protect against UVR-induced damage and the subsequent development of skin cancer. We propose that this initial protection is achieved through its anti-oxidant role resulting in reduced oxidative stress, reduced apoptosis, reduced NFkappaB activation and enhanced repair of DNA damage. However, once UVR-induced neoplasia has occurred, the cancer cells can hijack metallothionein's protective functions, resulting in increased tumour progression and malignancy. These two discordant sets of attributes are context-dependent, and represent the two faces of metallothionein.