Misao R, Nakanishi Y, Fujimoto J, Tamaya T
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Cancer Res. 1997 Dec 15;57(24):5579-83.
We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine endometrial cancer using the reverse transcription-PCR-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved that 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 this variant might be different from that of the SHBG wild type. In uterine endometrial cancers, the wild-type mRNA levels significantly (P < 0.01) decreased, and the ratio of the SHBG variant to wild-type mRNA levels (P < 0.01) increased with the advance of histological dedifferentiation. These results suggest that dedifferentiation of endometrial cancers might induce a reduction in their estrogen-dependent properties via intracellular SHBG.
我们通过逆转录 - PCR - Southern印迹和DNA测序分析,证实了性激素结合球蛋白(SHBG)外显子VII剪接变体mRNA在人子宫内膜癌中的细胞内表达。对缺失碱基对的分析证明,它们对应于整个外显子VII,该外显子被认为编码类固醇结合位点的一部分,这表明该变体的类固醇结合亲和力可能与SHBG野生型不同。在子宫内膜癌中,随着组织学去分化的进展,野生型mRNA水平显著降低(P < 0.01),而SHBG变体与野生型mRNA水平的比值增加(P < 0.01)。这些结果表明,子宫内膜癌的去分化可能通过细胞内SHBG诱导其雌激素依赖性特性的降低。