HUMAN LUNG, BLADDER AND HEAD AND NECK TUMORS AS COMPARED TO THEIR ADJACENT NORMAL-TISSUES HAVE ELEVATED AP-1 ACTIVITY AND RECOGNIZE SEQUENCE ELEMENTS OF HIV-1 LTR

Abstract

We have previously reported the specific binding of nuclear factor AP-1 isolated from human breast MDA MB 468 and HeLa cervical tumor cell lines to oligonucleotides complementary to three newly elucidated sequences within the HIV-1 LTR. These synthesized oligonucleotides, which bear high homology to the AP-1 recognition sequence, were used in the present study in gel retardation assays together with unfractionated nuclear protein extracts from human lung, bladder and head and neck tumors and adjacent normal tissue to study the role of the AP-1 protein in the regulation of HIV-1 expression. We found increased binding of AP-1 to these oligonucleotides in 9/12 lung tumors, 9/14 bladder tumors and 7/7 head and neck tumors as compared to adjacent normal tissues. This confirms previous results obtained when using MDA MB 468 and HeLa nuclear protein extracts. These results indicate that, AP-1 could be contributing to the HIV-1 transcriptional regulation through its interaction with the AP-I binding sites of HIV-I LTR.