Expression of the O6-alkylguanine-DNA alkyltransferase gene is elevated in human breast tumor cells

In tumors, resistance to chemotherapeutic drugs that alkylate the O-6 position of guanine correlates with the levels of the DNA repair protein, O-6-alkylguanine DNA alkyltransferase (AGT). The expression of AGT gene in human breast tumors was evaluated at the level of the single cell, to better understand the distribution of alkylation resistant cells within the tumor. Compared to normal breast ductal cells, the level of ACT expression in the breast tumor cells increased 2-fold. There was no significant association between AGT expression and tumor grade and metastatic malignancy. The up-regulation of AGT was not directly linked to the expression of cyclins D1 and D3, estrogen receptor; p53 and c-erbB-2, genes involved in cell cycle regulation and tumor growth. The elevated expression of ACT in human breast ductal carcinoma cells appeared to be a general characteristic of breast tumors, and suggests that prior treatment with analogs of O-6-alkylguanine that inactivate AGT protein, should render the ACT expressing tumor cells sensitive to drugs that alkylate O-6-guanine.