DOMINANT EXPRESSION OF SEX-HORMONE-BINDING-GLOBULIN EXON-7 SPLICING VARIANT OVER WILD-TYPE MESSENGER-RNA IN HUMAN OVARIAN CANCERS

The intracellular expression of sex-hormone-binding-globulin(SHBG) exo n-7-splicing-variant mRNA in human ovarian cancers was demonstrated by reverse-transcription/ polymerase-chain-reaction, Southern-blot and D NA-sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon 7, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-bi nding affinity of this variant might be different from that of the SHB G wild type. SHBG wild-type and variant mRNA was detected in all norma l ovaries and in benign and malignant ovarian tumors analyzed. There w ere no significant differences in mean SHBG wild type and variant mRNA levels among the 3 types of tissue, but the ratio of SHBG exon-7-spli cing-variant to wild-type mRNA level in ovarian cancers was significan tly higher (p < 0.05) than that in normal ovaries, with over-expressio n in some benign tumors. SHBG mRNA levels and the ratio of SHBG varian t to wild-type mRNA was not associated with histological classificatio n or clinical stages of ovarian cancers. These results suggest that ov er-expression of SHBG-exon 7-splicing-variant mRNA to the wild type mi ght indicate the potential for neoplastic transformation. (C) 1998 Wil ey-Liss, Inc.