Role of metallothionein in cisplatin sensitivity of germ-cell tumours.

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Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer DT, Mulder NH

Role of metallothionein in cisplatin sensitivity of germ-cell tumours.

Int J Cancer. 2000 Mar 15;85(6):777-81.

PubMed ID

10709094 [ View in PubMed

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Abstract

Cisplatin (CDDP) is an extremely active drug in the treatment of germ-cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell-tumour and 3 colon-carcinoma cell lines. Major components of the sulfhydryl groups are glutathione and metallothionein (MT). We further investigated a possible role of MT in the CDDP sensitivity of germ-cell tumours. MT levels and functionality of the germ-cell-tumour and colon-carcinoma cell lines were found to be inversely correlated with CDDP sensitivity. No difference in sub-cellular localization of MT could be observed among the types of cell lines. In agreement with the in vitro data, immunohistochemical detection of MT was high in 11/14 primary human germ-cell tumours and low in 7/7 human colon carcinomas. MT-protein expression in primary germ-cell tumours did not discriminate between responding and non-responding patients. As compared with the primary tumours, MT-protein expression decreased in 5/7 post-chemotherapy residual vital tumours or remained undetectable (2/7). MT-protein expression in the germ-cell tumours was not related to total p53-protein expression. In summary, over-expression of MT was found in germ-cell tumours, both in cell lines and in human tumours. Although MT-protein over-expression seems to be associated with the CDDP sensitivity of germ-cell tumours, MT-protein expression in primary germ-cell tumours did not differ between responding and non-responding patients and therefore cannot be used to predict response to chemotherapy.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cisplatin	Metallothionein-1A	Protein	Humans	Unknown	Substrate	Details
Cisplatin	Metallothionein-2	Protein	Humans	Unknown	Substrate	Details