The identification of differentially expressed cell cycle -related genes in breast and colon cancer cell lines in response to chemotherapeutic drugs

Rupnarain, Charleen

The identification of differentially expressed cell cycle -related genes in breast and colon cancer cell lines in response to chemotherapeutic drugs

dc.contributor.author	Rupnarain, Charleen
dc.date.accessioned	2010-01-27T11:15:07Z
dc.date.available	2010-01-27T11:15:07Z
dc.date.issued	2010-01-27T11:15:07Z
dc.department	Internal Medicine
dc.department	Oncology
dc.description	Thesis (Ph. D.), Faculty of Health Sciences, University of the Witwatersrand, 2009	en_US
dc.description.abstract	With the high prevalence and high mortality rate of cancer in the global community, it is increasingly essential to accelerate our understanding of the disease, to identify new genetic targets for therapy, and to pursue avenues for improving on the therapies in development and in current use. The aim of this study is to identify cell cycle-related genes whose expression is influenced by the chemotherapeutic drugs curcumin, SAHA, lycopene and thalidomide in breast and colon cancer and normal cell lines. These drugs are currently not in clinical use for cancer in South Africa, and while there have been investigative studies of these chemotherapeutic agents, this study aims to identify the specific genes that are influenced by the drugs. The result of this is that several genes that were not previously documented as targets of these drugs are highlighted. The cell cycle pathway is the area of focus as loss of regulation in the cell cycle is one of the important factors involved in promoting cancer initiation and progression. In the first instance, flow cytometry was used to identify optimal drug concentrations relative to the cell cycle stages. Following this, alterations in gene expression were assessed using a PCR-based differential display after each drug treatment. Subsequently, a more focussed approach was taken in a PCR-array analysis of panels of cell cyclerelated genes. A subset of genes is identified that is implicated in oncogenic transformation in breast cancer. This has the potential to inhibit the genetic pathways involved in breast malignancy by providing targets that perhaps may not be manipulated in current therapies. The gene expression studies here suggest that lycopene and thalidomide function in inhibiting this transformation, and play significant roles in suppressing the oncogenic state of breast cancer. Curcumin and SAHA also exhibit important functions in inhibiting tumourigenesis in colon cancer. While the results propose that the drugs have clear roles in inhibiting breast and colon cancer, they are also implicated in promoting cancer. This research has defined the genes that must be carefully monitored during drug administering as they may promote these and other cancers. The availability of these results to researchers will aid in selecting the criteria for assessing the success rate of these drugs.	en_US
dc.identifier.uri	http://hdl.handle.net/10539/7479
dc.language.iso	en	en_US
dc.subject	chemotherapeutic drugs	en_US
dc.subject	genes	en_US
dc.subject	cells	en_US
dc.subject	cancer	en_US
dc.title	The identification of differentially expressed cell cycle -related genes in breast and colon cancer cell lines in response to chemotherapeutic drugs	en_US
dc.type	Thesis	en_US