Expression of the O6-alkylguanine-DNA alkyltransferase gene is elevated in human breast tumor cells.
In tumors, resistance to chemotherapeutic drugs that alkylate the O6 position of guanine correlates with the levels of the DNA repair protein, O6-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 AGT 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 AGT in human breast ductal carcinoma cells appeared to be a general characteristic of breast tumors, and suggests that prior treatment with analogs of O6-alkylguanine that inactivate AGT protein, should render the AGT expressing tumor cells sensitive to drugs that alkylate O6-guanine.
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Division of Radiobiology, College of Medicine, Ohio State University, Columbus 43210, USA.
D'Ambrosio
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D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D019938:Cyclin D1 / Q000096:biosynthesis; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis
D019938:Cyclin D1; D056743:Cyclin D3; D016213:Cyclins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C534696:CCND3 protein, human