Relatively high expression ratio of sex hormone-binding globulin exon VII splicing variant to wild-type mRNA in human uterine cervical cancers.

We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine cervical cancer using reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of the variant protein might be different from that of the wild-type SHBG. In uterine cervical cancers, the wild-type mRNA levels were lower (P<0.01) and the ratio of the SHBG variant to wild-type mRNA levels was higher (P<0.01) than in the normal cervix. In cervical adenocarcinomas, the wild-type mRNA levels were higher (P<0.05) and the ratio of the SHBG variant to wild-type mRNA levels was lower (P<0.05) than in cervical keratinizing squamous cell carcinomas. There was no difference in expression among the clinical stages of cervical cancers. These results suggest that a relative increase of intracellular variant SHBG protein in human uterine cervical cancers might be involved in the disruption of the normal estrogen dependence.