The role of metallothionein in oncogenesis and cancer prognosis.
The antiapoptotic, antioxidant, proliferative, and angiogenic effects of metallothionein (MT)-I+II has resulted in increased focus on their role in oncogenesis, tumor progression, therapy response, and patient prognosis. Studies have reported increased expression of MT-I+II mRNA and protein in various human cancers; such as breast, kidney, lung, nasopharynx, ovary, prostate, salivary gland, testes, urinary bladder, cervical, endometrial, skin carcinoma, melanoma, acute lymphoblastic leukemia (ALL), and pancreatic cancers, where MT-I+II expression is sometimes correlated to higher tumor grade/stage, chemotherapy/radiation resistance, and poor prognosis. However, MT-I+II are downregulated in other types of tumors (e.g. hepatocellular, gastric, colorectal, central nervous system (CNS), and thyroid cancers) where MT-I+II is either inversely correlated or unrelated to mortality. Large discrepancies exist between different tumor types, and no distinct and reliable association exists between MT-I+II expression in tumor tissues and prognosis and therapy resistance. Furthermore, a parallel has been drawn between MT-I+II expression as a potential marker for prognosis, and MT-I+II's role as oncogenic factors, without any direct evidence supporting such a parallel. This review aims at discussing the role of MT-I+II both as a prognostic marker for survival and therapy response, as well as for the hypothesized role of MT-I+II as causal oncogenes.
Section of Neuroprotection, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. majsan_43@yahoo.se
Mie Ø
MØ
Pedersen
Agnete
A
Larsen
Meredin
M
Stoltenberg
Milena
M
Penkowa
D014408:Biomarkers, Tumor / Q000737:chemistry; D006801:Humans; D008668:Metallothionein / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D009369:Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology*; D011379:Prognosis
D014408:Biomarkers, Tumor; D008668:Metallothionein