Unravelling the molecular details of zinc homeostasis in breast and prostate cancer cells

Abstract

Breast and prostate cancers are the prominent global burden for not only the patients, but also the health systems of governments. The intricacy of the cancer development and pathology for these two kinds of cancers is being actively studied in the research laboratories around the world, breakthroughs of which contribute to the anticancer drug development and treatment. One intriguing aspect of breast and prostate cancers is their contrasting intracellular zinc levels, i.e. the higher intracellular zinc level in breast cancer cells compared to the normal counterparts whilst lower intracellular zinc level in prostate cancer cells against the normal prostate epithelial cells. This project seeks to uncover the molecular details related to the zinc homeostasis of breast and prostate cancer cells by proteomics and gene profiling with quantitative real time polymerase chain reaction (qRT-PCR).

The top-down proteomics was carried out to profile the protein expressions of breast cancerous and normal cells (MCF-7 and MCF-10A) under zinc treatment conditions in a time course. The same proteomic approach was also applied to the prostate cancerous and non-cancerous cells (PC3 and RWPE-1). The cells were subjected to extracellular zinc exposure for 0, 30 and 120 min (T0, T30 and T120) as well as no extracellular zinc exposure. The protein samples from each treatment timepoint were extracted with the use of a urea/thiourea CHAPS [3-(3-cholamidopropyl) dimethylammonio)-1-propanesulfonate] lysis buffer. The proteins were separated by 2D gel electrophoresis based on the isoelectric point (1st dimension) and molecular weight (2nd dimension). The separated individual protein spots were analysed for identifying spots of differential expression. The differentially expressed protein spots were further identified through liquid chromatography-tandem mass spectrometry and ProteinLynx Global Server database.

This study uncovered the differentially expressed proteins in normal and cancerous breast and prostate cells in the context of change in extracellular zinc level. The findings provide potential therapeutic targets for anticancer drug development and significant insights into our understanding of the effect of zinc on both breast and prostate cancer cells.

Date of Award	2024
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Ming Wu (Supervisor) & Chandra S. Malladi (Supervisor)