Metallothionein expression in human neoplasia

Abstract

The metallothionein family is a class of low-molecular-weight, cysteine-rich proteins with high affinity for metal ions. Four major isoforms (metallothionein-1, -2, -3, and -4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the expression of metallothionein in different human tumours and its correlation with histopathological variables, tumour cell proliferation or apoptosis, resistance to radiation or chemotherapy, patient survival and prognosis. A variable profile of metallothionein and its isoforms' expression has been observed in different cancer types. Although metallothionein expression has been implicated in carcinogenic evolution, its use as a marker of tumour differentiation, cell proliferation and prognosis predictor remains unclear. Detailed studies focused on the expression of metallothionein isoforms and isotypes in different tumour types could elucidate the role of this group of proteins in the carcinogenic process, delineating its possible clinical significance for the management of patients.

Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells

“…Two of these genes were the metallothioneins, MT1E and MT1X. This class of genes has previously been implicated with human cancers (Theocharis et al, 2004). The third gene was the cytokine IL-1a.…”

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

“…Although MT participate in the carcinogenic process, their use as a potential marker for tumour differentiation or cell proliferation, as well as a marker of poor prognosis remains controversial (Cherian et al, 2003;Theocharis et al, 2004). In the last decade, several reports disclosed MT overexpression as a useful prognostic factor for tumour progression and drug resistance in a variety of cancers such as ovarian cancer (Surowiak et al, 2005), renal cell carcinoma (Mitropoulos et al, 2005), breast cancer (Jin et al, 2004), non-small-cell lung carcinomas (Dziegiel et al, 2004), acute lymphoblastic leukaemia (Sauerbrey et al, 1994), pancreatic carcinoma (Ohshio et al, 1996) or carcinoma of the gallbladder (Shukla et al, 1998).…”

Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

“…12,14 The role and the expression of MTs in human tumors have been extensively investigated, but the results are often contradictory among different cancer types; therefore, the real contribution of these important molecules to malignant transformation has not yet been clarified. 15 MT overexpression has been observed in several tumors such as melanoma, breast and lung cancer, and in some cases has been associated with a poor prognosis 16,17 and with resistance to treatments. 18 Conversely, other tumor types, such as colorectal cancer and hepatocellular carcinoma, show a downregulation of MT expression during cancer progression.…”