Molecular insights into the zinc homeostasis of breast and prostate cancer cells

Abstract

Zinc ion (Zn2+) is essential to life as a structural or catalytic component of proteins. The cell has developed an elaborate molecular network over the extensive evolutionary timeline to maintain zinc homeostasis. Any disruption of such a network will lead to zinc dyshomeostasis, resulting in health problems such as cancers. Zinc dyshomeostasis is an intriguing phenomenon in breast and prostate cancers, with breast cancer cells exhibiting higher intracellular Zn2+ levels compared to their corresponding normal epithelial cells, in contrast to the low Zn2+ levels in prostate cancer cells compared to the normal prostate counterpart. Such contrasting zinc profiles of breast and prostate cancer cells provide an avenue for this PhD project to investigate the Zn2+ homeostasis of breast and prostate cancer cells by a systematic approach of gene profiling via quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence confocal microscopy and proteomic analysis with a panel of cell lines including two breast cancer cell lines (MCF-7, MDA-MB-231), two prostate cancer cell lines (PC3 and DU145), along with normal breast epithelial and prostate epithelial cell lines (MCF10A, RWPE-1). A systematic approach of gene profiling, immunofluorescence confocal microscopy and proteomic analysis was carried out, using a panel of cell lines which include two breast cancer cell lines (MCF-7, MDA-MB-231), two prostate cancer cell lines (PC3 and DU145), along with normal breast epithelial and prostate epithelial cell lines (MCF10A, RWPE-1). The systematic experimental approach of this project returned the meaningful findings, which enhances our knowledge and understanding of the zinc homeostasis in breast and prostate cancer cells. The molecular clues uncovered here should not only contribute to the elucidation of molecular network of zinc homeostasis but should also serve as potential molecular targets for anti-cancer drug development. As zinc dyshomeostasis is increasingly linked to the development and progression of cancers such as breast and prostate cancers, and zinc is emerging as an important signalling messenger in normal and cancerous cells, the findings of this project provide avenues for further studies on breast and prostate cancers.

Date of Award	2023
Original language	English