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Student Project Details
Student Research

For general student queries on working at the LICR Melbourne Centre please contact the Student Advisor, A.Prof Weisan Chen (03 9496 3700) or email

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BSc.(Hons) Project Details
Oncogenic Transcription Laboratory
icon Role of villin in colon cancer metastasis.
icon Mechanisms of HDAC3 gene regulation in colon cancer
 
Role of villin in colon cancer metastasis.
Research Group
Oncogenic Transcription Laboratory
Available As
BSc(Hons)
Supervisor(s)
John Mariadason
Further Information

Project Details

We have recently discovered a subset of colon cancers in which the cytoskeletal protein, villin, is completely absent. Remarkably, loss of villin occurs selectively in colon cancers with a characteristic known as “microsatellite instability” or MSI. Cancers with this characteristic are less likely to metastasize and have a better outcome. This honours project will examine whether the villin protein is required for tumour cell metastasis and whether its loss is responsible for the lower metastatic rates of MSI colon cancers. The project will involve working with colon cancer cell lines and reintroduction of the villin gene into villin- negative cells. The effect of villin on migration and metastasis of these cells will then be studied in vitro and in a mouse model. The project will also involve working with villin knockout mice to study the role of villin on normal intestinal cell migration. The significance of this study is that demonstration of a pro-metastatic role for villin in colon cancer will provide novel insight into the metastatic process and identify a novel candidate for targeted treatment. The project will provide the student with a sound introduction to fundamental concepts in cancer biology, and experience in cell biology, molecular biology and animal (mouse) studies. This Hons project will be conducted in the Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg.

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Mechanisms of HDAC3 gene regulation in colon cancer
Research Group
Oncogenic Transcription Laboratory
Available As
BSc(Hons)
Supervisor(s)
John Mariadason
Further Information

Project Details

Colon Cancer is driven by mutations in key genes which result in excessive cell proliferation. Identification of the genes which drive the excessive growth of colon cancer cells can identify new targets for treatment. We have been studying a gene called Histone deacetylase 3 (HDAC3), which is highly expressed in colon tumours and which promotes growth of colon cancer cells. The goal of this project is to understand how HDAC3 expression is controlled in colon cancer cells. Specifically, the project will determine the role the MYC-MAD-MAX family of transcription factors play in this process. The project will have a strong molecular focus and will involve creating a series of HDAC3 promoter constructs to identify the important regulatory regions within the HDAC3 promoter. The role of MYC in regulating HDAC3 expression will also be investigated by silencing MYC using siRNA, and reciprocally, by MYC overexpression. This project will provide a comprehensive introduction into key concepts in colon cancer biology and experience in molecular and cell biology techniques including cloning, transfection, cell culture, siRNA, ChIP, western blotting and real-time PCR. This Hons project will be conducted in the Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg.

References

HDACs and HDAC inhibitors in colon cancer. JM Mariadason. Epigenetics. 2008 Jan-Feb;3(1):28-37.

HDAC4 promotes growth of colon cancer cells via repression of p21. AJ Wilson, D-S Byun, S Nasser, LB Murray, K Ayyanar , D Arango, M Figueroa, A Melnick, G Kao, LH. Augenlicht and JM. Mariadason. Mol. Biol. Cell. 2008. 19: 4062-4075.

Class I Histone deacetylases are upregulated in human colonic tumors and are linked to reduced cell differentiation in vivo and in vitro. AJ Wilson, DS Byun, HJ Smartt, K L’Italien, Y Sowa, D Arango, LH Augenlicht and JM Mariadason. J. Biol. Chem. 2006 May 12;281(19):13548-58.

PIK3CA/PTEN mutation status predicts response of colon cancer cells to cetuximab. Jhawer, M., Goel, S., Wilson, A.J., Montagna, C., Ling, Y.H., Byun, D.S., Nasser, S., Arango, D., Shin, J., Klampfer, L., Augenlicht, L.H., Soler, R.P., and Mariadason, J.M. Cancer Res, 68(6): p. 1953-61 2008

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