Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Cancer is a progressive disease in which a tumor cell temporally develops q ualitatively new transformation related phenotypes or a further elaboration of existing transformation associated properties. Subtraction hybridizatio n identified a novel gene associated with transformation progression in mut ant adenovirus type 5, H5ts125, transformed rat embryo cells, progression e levated gene-3 (PEG-3). To define the mechanism by which expression of PEG- 3 is enhanced as a function of cancer progression a 5'-flanking promoter re gion of similar to 2.0-kb, PEG-Prom, was Isolated, cloned and characterized . The full-length and various mutated regions of the PEG-From mere linked t o a luciferase reporter construct and evaluated for promoter activity durin g cancer progression. These assays demonstrate a requirement for API and PE A3 sites adjacent to the TATA bos region of PEG-3 in mediating basal promot er activity and the enhanced expression of PEG-3 in progressed H5ts125-tran sformed rat embryo cells. An involvement of AP1 and PF Lambda 3 in PEG3 reg ulation was also confirmed by electrophoretic mobility shift assays (EMSA) and transfection studies with cJun and PEA3 expression vectors, Our finding s document the importance of both AP1 and PEA3 transcription factors in med iating basal and elevated expression of PEG3 in H5ts125-transformed rat emb ryo cells displaying an aggressive and progressed cancer phenotype.