Professor, Department of Oncology
Keywords: Metallothionein and resistance to radiation and chemotherapeutic drug treatment
Description of Research Activities
The development of resistance to radiation or chemotherapy by malignant cells is a significant cause of failure of cancer therapy. Metallothionein (MTs) are a class of proteins that have been associated with cellular resistance to these agents and with homeostasis of essential metals within cells. We hypothesize that MTs play a critical role in sequestering or donating essential metals (zinc and copper) to proteins that include hormone receptors, transcription factors, and enzymes regulating reactive oxygen molecules. We are investigating this potential role by transfecting human normal and tumour cells with transcriptionally active rodent and human metallothionein genes to allow constitutive expression of MT, or vectors expressing "antisense" RNA to down-regulate MT. Mice and cultured cells with genetically ablated MT genes (MT knockouts) are also being used to explore the function of MT. The effect on cell viability and growth, cellular drug resistance, apoptosis, differentiation capacity, and susceptibility to chemical and radiation-induced mutation is being investigated.
(Funded by CIHR)
Thymidylate Synthase (TS) and Cell Growth and Drug Resistance:
The role of thymidylate synthase in cell growth and chemotherapeutic drug resistance, novel effects on TS gene transcription in response to antisense nucleic acids, and the usefulness of downregulation of TS using antisense oligodeoxynucleotides is being explored.
(Funded by Zeneca Pharma Canada, Inc., with Mark Vincent).