Study on carcinogenesis of breast cancer with SHBG(Sex hormone binding globulin) : Study on SHBG as a RISK FACTOR of breast cancer

我们发现了一种新的调节正常绝经前妇女血浆游离雌二醇浓度的系统。具有生物活性的游离雌二醇浓度受血浆总雌二醇浓度和SHBG的调节。SHBG对17&lt；β-雌二醇的高结合能力与血浆游离雌二醇水平高和激素依赖型乳腺癌的存在有关。雌激素可激活正常乳腺细胞的ras、myc和fos原癌基因，也可激活乳腺癌细胞的ras、myc和fos癌基因。在MCF-7人乳腺癌细胞中，雌激素除了激活上述三种癌基因外，还激活了EGFR基因和雌激素受体基因的RNA活性，而抗雌激素药物三苯氧胺则抑制了上述两种受体基因和癌基因(ras、myc和fos癌基因)的表达。这些结果表明，SHBG上的高雌二醇结合量和高水平的血浆和胞浆中游离雌二醇是一个重要的危险因素，在人类乳腺癌的发生中起着重要的作用。

We found a novel regulation system of plasma unbound estradiol concentration in normal premenopausal women. Concentration of unbound estradiol which has biological activity was regulated by both plasma total estradiol concentration and SHBG. High binding capacity of SHBG for 17 <beta> -estradiol was associated with high levels of plasma unbound estradiol and the presence of hormone dependent breast cancer. Estradiol activated ras, myc, and fos proto-oncogenes of normal breast cells,and also activated ras, myc, and fos oncogenes of breast cancer cells in primary culture. Estradiol activated RNA activities of EGFR ( Epidermal growth factor receptor) gene and estrogen receptor gene in addition of activation of above three kinds of oncogenes in MCF 7 human breast cancer cells.On the other hand, anti-estrogen ( Tamoxifen ) suppressed above two kinds of receptor genes, and oncogenes ( ras, myc, and fos oncogenes ). These results indicate that high estradiol binding capacity on SHBG with high levels of unbound estradiol in plasma and cytosol is an important RISK FACTOR and has an important role in the carcinogenesis of human breast cancer.