Differential interaction of cisplatin with the HIV-1 long terminal repeat in a resistant ovarian carcinoma cell line.
Zoumpourlis V., Kerr DJ., Spandidos DA.
We constructed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequences of HIV-1 linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in a human ovarian cancer cell line A2780 and in a cisplatin resistant variant 2780CP, and obtained stable geneticin resistant A27HIV1-1 and 27CPHIV1-1 cells, respectively. Both transfectant cells expressed CAT activity from the HIV LTR promoter. The response to the anti-neoplastic drug cisplatin was studied on the LTR regulated CAT activity in both cell lines. It was found that cisplatin at 2.5 x 10(-5) M concentration stimulates the expression of CAT by 26-fold from the HIV LTR in A27HIV1-1, but requires a concentration of 5 x 10(-5) M to enhance expression by 4.1-fold in the cisplatin resistant 27CPHIV1-1 cells. Carboplatin, over a range of concentrations (1 x 10(-6) to 1 x 10(-4) M), does not stimulate expression of CAT from the HIV-1 LTR in either of the transfected cells.