Content of Gonadotropins in Cultured Human Malignant Cells and Effects of Sodium Butyrate Treatment on Gonadotropin Secretion by HeLa Cells

Abstract

Twenty-one of 82 human cell lines examined for production of human chorionic gonadotropin and its subunits (HCG-α and HCG-β) produced either one or both subunits at some phase in their growth. Of these, 14 produced an excess amount of free α subunit, and seven produced HCG-β or complete HCG without evidence for free α subunit synthesis. Five of the HCG-producing cell lines also contained or secreted the β subunit of human luteinizing hormone. CBT cells derived from a glioblastoma multiforme and JAR choriocarcinoma cells secreted significant amounts of the β subunit of human luteinizing hormone, while three other cell lines (breast carcinoma MCF-7, HeLa S₃, and melanoma A375) produced small amounts of the β subunit of human luteinizing hormone but did not appear to secrete it. Two cell lines (the melanoma line A375 and the SV40-transformed line SV80) appeared to contain small amounts of human follicle-stimulating hormone. Sodium butyrate caused a 40-fold induction in the secretion of both HCG-α and HCG-β by HeLa S₃ cells, but the total amount of HCG-α secretion induced was 800-fold greater than that of HCG-β. Induction was blocked by actinomycin D (1 µg/ml) and cycloheximide (5 µg/ml) but was not affected by 1-β-d-arabinofuranosylcytosine at a concentration (5 µg/ml) that blocked DNA synthesis 99%. These results indicate that a number of malignant human cell lines produce the subunits of both placental and pituitary gonadotropins and that there is frequently an excess secretion of the free α subunit common to these hormones.