BASIC FIBROBLAST GROWTH-FACTOR AND ITS RECEPTOR MESSENGER RIBONUCLEIC-ACIDS ARE EXPRESSED IN HUMAN OVARIAN EPITHELIAL NEOPLASMS

OBJECTIVE: Our purpose was to determine whether basic fibroblast growt h factor is present in, and synthesized by, human ovarian epithelial n eoplasms and to evaluate the expression of gene for the basic fibrobla st growth factor receptor. STUDY DESIGN: The synthesis of basic fibrob last growth factor and its receptor was investigated in seven primary human ovarian epithelial neoplasms. Neoplastic tissues were homogenize d and the cytoplasmic extracts purified by heparin-sepharose chromatog raphy with a linear salt gradient of 0.6 to 3 mol/L sodium chloride in Tris-hydrochloric acid. The in situ synthesis of basic fibroblast gro wth factor and its receptor was demonstrated by polymerase chain react ion. Total ribonucleic acid was reverse transcribed and then amplified with two oligonucleotide primers specific for the bovine and human ba sic fibroblast growth factor gene and its human receptor gene. RESULTS : As assessed by both bioassay and radioimmunoassay a peak of basic fi broblast growth factor-like activity was present in all tumors in the chromatographic tractions eluted with 3 mol/L sodium chloride. The mit ogenic effect on bovine adrenocortical endothelial cell proliferation varied from 35% to 153% above control cultures. Levels of basic fibrob last growth factor-like immunoreactivity were between 4 and 33 ng/ml. Qualitatively similar results were obtained after purifying the cytopl asmic extract of dispersed human ovarian tumor cells. The mitogenic ef fect was completely abolished by a specific neutralizing anti-basic fi broblast growth factor antibody. Single major deoxyribonucleic acid ba nds of the expected size (354 and 661 bp) were detected in all tumors studied. The identity of this material with the human basic fibroblast growth factor sequence was confirmed by restriction enzyme analysis. CONCLUSION: These data demonstrate that both basic fibroblast growth f actor and its receptor are present in and synthesized by human ovarian tumor cells. Thus basic fibroblast growth factor might stimulate thei r abnormal proliferation through an autocrine mechanism.