Naomi Glarner Time-dependent Transcriptional Changes in a Breast Cancer Cell Line Caused by Hypoxia Master Thesis in Bioinformatics Advisors: Ingrid Hedenfalk and Markus Ringnér Abstract: Breast cancer is the most common form of malignant disease affecting women in the Western World. Nearly 50% of locally advanced breast cancers exhibit areas of hypoxia which is associated with poor prognosis. The aim of this project was to investigate the time dependency of transcriptional changes due to in vitro hypoxia treatment of a breast cancer cell line. cDNA microarrays containing 27,000 clones were used to analyze gene expression patterns at different time points of hypoxia treatment. A time series analysis of the microarray data was performed to reveal genes exhibiting specific patterns of expression. Hypoxia treatment affected the expression of genes involved in glucose metabolism, apoptosis, cell cycle progression and angiogenesis. Notably, the genes involved in glucose metabolism were induced earlier than cell cycle regulatory genes. Furthermore, Lysyl Oxidase-like 2, a gene recently implicated in breast cancer invasion, was strongly upregulated by the hypoxic treatment. This may be one of the several mechanisms by which hypoxia affects the malignant progression of tumors. March 2003 LU TP 03-06