AbstractsBiology & Animal Science

Amplification of several regions of chromosome 8q is frequently detected in breast tumors, and several genes located on this chromosome arm show increased expression in the tumors. One of these genes encodes ã-glutamyl hydrolase (GGH), a key enzyme in the metabolism of folate and many antifolate drugs used in cancer treatment. GGH is highly expressed in the basal-like subgroup of breast tumors, and furthermore in TP53 mutant tumors, which are overrepresented in the basal-like tumor subgroup. The basal-like tumors represent an aggressive disease entity associated with poor patient prognosis. Based on this, GGH can be hypothesized to be involved in the development of breast cancer. To explore the significance of GGH expression for specific cancer relevant phenotypes, the GGH expression in a breast tumor cell model was manipulated in this thesis. The cell line Sum102, which is a model for the basal-like breast tumor subtype, was selected for the experiments. Cell populations with reduced and overexpressed GGH levels were constructed separately, and the proliferation rate and sensitivity to chemotherapeutic drugs of the resulting cells were assayed. The results indicated that manipulation of GGH expression did not affect the proliferation rate of the cells. However, the cell populations with increased GGH expression showed increased sensitivity to 5-fluorouracil, and also a tendency to decreased sensitivity to doxorubicin. 5-Fluorouracil and doxorubicin are frequently used in breast cancer chemotherapy, and the indication that GGH can influence the sensitivity to these drugs should be further investigated.