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On PGC1alpha and mitochondrial status in parental and chemoresistant ovarian cancer cell lines

Barbachowska, Magdalena (2016) MOBT01 20161
Degree Projects in Molecular Biology
Popular Abstract
Epithelial ovarian carcinoma is a gynecological cancer with the highest death incidence worldwide. It is treated with surgery and chemotherapeutic drugs: platinum or taxane. However, around 80% of patients have disease progression into more aggressive and chemoresistant cancer. Mitochondria are structures inside both normal and cancer cells which are central to the cell´s metabolism by supplying energy and metabolites for growth. Mitochondria are also known to be involved in motility and in chemoresistance, but it is not clear how they do that. The functions of mitochondria are regulated by certain proteins. The research group has a cell line that is highly chemoresistant and which lacks one protein, named PGC1α, crucial for regulation of... (More)
Epithelial ovarian carcinoma is a gynecological cancer with the highest death incidence worldwide. It is treated with surgery and chemotherapeutic drugs: platinum or taxane. However, around 80% of patients have disease progression into more aggressive and chemoresistant cancer. Mitochondria are structures inside both normal and cancer cells which are central to the cell´s metabolism by supplying energy and metabolites for growth. Mitochondria are also known to be involved in motility and in chemoresistance, but it is not clear how they do that. The functions of mitochondria are regulated by certain proteins. The research group has a cell line that is highly chemoresistant and which lacks one protein, named PGC1α, crucial for regulation of mitochondrial function. These cells also had changes in the mitochondrial appearance and became more motile compared to a similar cell line that is less resistant.
Here, these cell lines were used to study the role of PGC1a in cell motility and metabolism. We compared the cells with respect to levels of proteins known to be present in motile and aggressive cells. We examined cell metabolism by investigating cell growth in different nutrients like glucose, glutamine, galactose or in the absence of those compounds, and examined mitochondrial function when cells were starved of nutrients. Furthermore, the effect on motility of drugs that could potentially increase the level of PGC1α was investigated. Finally, we examined if shutting down PGC1a in chemosensitive cells would lead to a changed mitochondrial appearance and increased motility. The results showed differences in cell metabolism in the cell lines which might mean that the resistant cells have greater abilities to adjust to different stresses compared to chemo-sensitive cells. We found that cis-platin resistant cells expressed proteins known to be needed for the cells to be motile and to be able to spread to other organs. However, we could not affect cell motility by any drug treatment. Moreover, when we targeted gene coding for PGC1a we observed changes in mitochondrial appearance. However, this did not affect cell motility.
The best way to fight your enemy is to know it better. This study helps to understand how cancer cells can move and spread to other organs, and why they are often very resistant to chemotherapy.

Supervisor: Dr. Maria Shoshan, Cancer Center Karolinska, Karolinska Institutet
Master´s Degree Project in Molecular Biology 60 credits, 2016
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Barbachowska, Magdalena
supervisor
organization
course
MOBT01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8891457
date added to LUP
2016-09-12 11:53:32
date last changed
2016-09-12 11:53:32
@misc{8891457,
  author       = {Barbachowska, Magdalena},
  language     = {eng},
  note         = {Student Paper},
  title        = {On PGC1alpha and mitochondrial status in parental and chemoresistant ovarian cancer cell lines},
  year         = {2016},
}