The Role of Metallothioneins in Carcinogenesis

Abstract

Due to their role in various cellular processes, metallothioneins have been studied in numerous benign and malignant lesions, in regard to carcinogenesis, and in tumor progression (Dziegiel 2004; Krizkova et al. 2009b, 2012; Pedersen et al. 2009; Pula et al. 2012; Fic et al. 2013). Although the role of MTs in tumor initiation and progression has been intensely studied, it is only recently that studies have allowed the elucidation of the tumor suppressory roles of some MT isoforms—such as of MT-1G in papillary thyroid cancer and the large intestine and MT-1E in melanomas (Ferrario et al. 2008; Faller et al. 2010; Arriaga et al. 2014). On the other hand, MT-2A has been shown to promote the progression of breast and non-small cell lung cancer (Jin et al. 2002; Lim et al. 2009; Lai et al. 2010; Werynska et al. 2013b). Lines of evidence indicate that MTs exert divergent expression patterns in normal tissue and tumors; for this reason, more detailed studies concentrated on each isoform, and not on MT-1 and MT-2 collectively, need to be conducted. Nevertheless, the results of many studies have identified the involvement of MTs in cancer cell proliferation (Jin et al. 2002), apoptosis (Krizkova et al. 2009b), invasiveness, and migration (Jin et al. 2001; Kim et al. 2011; Ryu et al. 2012), as well as on cancer cells sensitivity to various anticancer agents (Kondo et al. 1995a, b, 1997). In this chapter, the role of MT isoforms in the development and progression of various tumors, with special emphasis on their prognostic significance, will be summarized in an organ-specific manner.