Item – Theses Canada

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OCLC number
175281957
Link(s) to full text
LAC copy
LAC copy
Author
Falcioni, Lisa,1979-
Title
The role of the phosphatidylinositol-3 kinase-AKT pathway in determining radiation sensitivity in the breast cancer cell line MDA-MB 231.
Degree
M. Sc. -- Laurentian University, 2005
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2006]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
To study clinically advanced breast cancer, our laboratory previously generated a model system through fractionated radiation of MDA-MB 231 breast cancer cells. Subsequently, radio-resistant (R) and -sensitive (S) subclones were isolated from the fractionated population. Clonogenic assays showed that the R clone is approximately 10-fold more radioresistant than the S clone at 5 Gy. To better understand causal mechanisms through which the R clone gains more radioresistance, we analyzed the levels of mRNA using cDNA microarray assays. Our data suggests that the intrinsic gene expression patterns of the R and S clones are very similar, except for four genes, CCAAT/enhancer-binding protein delta ('C/EBP' [delta]), collagen type XI alpha-2 (' COL11A2'), TAR RNA-binding protein 2 ('TARBP2') and phosphatidylinositol 3 kinase regulatory 1 ('PI3KR1'), the gene encoding for p85[alpha], the regulatory subunit of phosphatidylinositol-3 kinase (PI-3K). We have since established that the PI-3K signal transduction pathway is rapidly activated in the R clone in response to 8 Gy, which is abrogated by the LY294002 PI-3K inhibitor. In addition, our data showed that the progression of the R clone cells through the cell cycle is affected by inhibition of the PI-3K/Akt pathway. We found evidence of an increase in differential gene expression between R and S clones following IR, suggesting the small intrinsic difference in gene expression between the R and S clones is further "amplified" following ionizing radiation treatment.
ISBN
0494100222
9780494100226