989. IAI.3B Promoter Is Ovarian Cancer Specific

Abstract

The IAI.3B gene was isolated using a polyclonal serum against a high molecular weight fraction derived from the pleural fluid of a patient with ovarian cancer. CA125 is overexpressed in ovarian cancer and widely used for monitoring this type of cancer. IAI.3B and CA125 exhibit very similar patterns of expression in a wide variety of normal and ovarian cancer tissues. The deduced peptide sequence of IAI.3B encompasses a B-box/coiled coil motif present in many genes with transformation potential. In the present study, we cloned and characterized the promoter element of the IAI.3B gene. In real-time RT-PCR analysis, ovarian cancer cells (PA-1, RMG-1, 420, OCC1, OVCAR3) had at least 10-100-fold higher levels of IAI.3B mRNA than squamous cell carcinoma cells (ME-180, EBC-1 and HSC-5) and normal ovarian epithelial cells (NOE1, NOE2 and NOE3). Exon 1A was not transcribed in ovarian cancer cells. No TATA box was found. Transient transfection experiments showed that the DNA segment located between -1816 and -1 bp resulted in preferential expression in ovarian cancer cells with negligible expression in squamous cell carcinoma and normal cells. The promoter activity of IAI.3B was almost the same as that of cytomegalovirus and an order of magnitude higher than those of midkine and cyclooxygenase-2 in ovarian cancer cells. From these results, IAI.3B promoter might be specific for ovarian cancer and provide a potential for the development of ovarian cancer gene therapy.