ANDROGEN RESPONSIVENESS OF THE NEW HUMAN ENDOMETRIAL CANCER CELL-LINEMFE-296

MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a mo derately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were obs erved. DNA analyses confirmed the genetic identity of the cell line an d the patient from whom the cell line was derived. Proliferation of MF E-296 cells was inhibited by the progestin R5020 and the androgen dihy drotestosterone (DHT). The inhibition of proliferation by DHT was anta gonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 bindi ng sites per cell using a whole-cell assay (K-D = 0.05 nM) and 30 fmol /mg protein with the dextran charcoal method; 7 fmol/mg protein of pro gesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as d emonstrated by transfection experiments with a reporter-gene construct , containing an androgen-responsive element. In MFE-296 cells the cont ent of the androgen receptor was up-regulated by its own ligand. (C) 1 994 Wiley-Liss, Inc.