Identification of Novel Cancer-Associated Protein Kinases

Overview

Topic status: We're looking for students to study this topic.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in Australian men. Patients at advanced stage are usually treated with hormone ablation therapy. Unfortunately, the disease usually relapses and becomes metastatic hormone-refractory prostate cancer (HRPC), a terminal stage that is currently untreatable. Identifying the molecular mechanisms responsible for the development of metastatic HRPC is crucial for the design of specific therapy against this disease.

A highly innovative loss-of-function screening using the Lentiviral-based short hairpin RNA (shRNA) library has been performed in our laboratory. This library expresses shRNAs that target the mRNAs of the 656 genes (4-5 different shRNA sequences per gene) which encode the whole human kinase family. Using this approach we have identified a number of protein kinases which are associated with the growth and survival of prostate cancer cells.

The goal of this study is to characterize the novel functional role of these kinases in the development of HRPC, which may lead to the identification of novel anti-cancer therapeutic target for the treatment of prostate cancer.

Hypothesis

Aberrant activation of cancer-associated protein kinases contributes to the development of HRPC.

  • Aim 1: Examine the expression profile of candidate kinases in human prostate cancer cell lines and tumor tissues
  • Aim 2: Characterise the function of candidate kinases in the development of HRPC
  • Aim 3: Study if inactivation of candidate protein kinases affects the growth of HRPC in vitro and in vivo

Methods and techniques that will be developed in the course of this project include:

  • cell culture
  • cell proliferation and viability assays
  • confocal microscopy
  • DNA cloning and protein purification
  • in vitro protein kinase assay
  • mouse prostate cancer xenograft model
  • live animal imaging
  • immunohistochemistry.

Duration of project

14 Nov to 23 Dec 2011

Number of hours

6 hours per day

Study level
PhD
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact
Please contact the supervisor.