Study of endocrinological contribution for invasion and metastasis in gynecological cancers

孕激素难治性雌激素依赖癌基因c-Ha-ras、c-fos和c-jun在子宫内膜癌中的表达被认为是一种转化表型。在女性生殖道癌症的进展过程中，雌激素受体外显子5剪接变异体（ER E5SV）作为转录激活因子的相对过表达和孕激素受体形式a （PR-A）作为转录抑制因子的表达受损可能有助于癌症的转移。此外，雌激素可促进部分子宫内膜癌侵袭转移的多个步骤，黄体酮可抑制雌激素相关事件，尤其是肿瘤源性血管生成。肿瘤生长过程中对孕激素的不规则反应可能与PR-A表达受损有关。孕激素受体形式B （PR-B）的显性表达而没有PR-A转录抑制的状态与某些肿瘤的发生有关，另一方面，在pr突变的女性生殖道癌症中，黄体酮对肿瘤源性血管生成是否有效尚不清楚。最有可能的是，黄体酮治疗作为抗血管生成治疗在pr突变的肿瘤中效果较差。本文提出的数据应该促使我们尝试基因疗法，将中和类固醇受体基因表达作为治疗女性生殖道癌症的一种方法。同时，各种抗血管生成抑制剂必须用于黄体酮难治性和黄体酮依赖性肿瘤。

Expression of the progesterone-refractory estrogen-dependent oncogenes c-Ha-ras, c-fos and c-jun in uterine endometrial cancers is recognized as a transformed phenotype. During advancement of female genital tract cancers, relative overexpression of estrogen receptor exon 5 splicing variant (ER E5SV) as a transcriptional activator and damaged expression of progesterone receptor form A (PR-A) as a transcriptional repressor might contribute to metastasis of the cancers. Furthermore, estrogen might enhance various steps of invasion and metastasis of some uterine endometrial cancers, and progestin could inhibit the estrogen-related events, especially tumor-derived angiogenesis. The irregular response to progestins in tumor growth might be caused by the damage to PR-A expression. The status of progesterone receptor form B (PR-B) dominant expression without PR-A transcriptional repression relates to some tumorigenesis, On the other hand, it is not clear whether progestin is effective on the tumor derived-angiogenesis in PR-mutated female genital tract cancers or not. Most Likely, progestin treatment as an anti-angiogenic therapy would be less effective in the PR-mutated tumors. The data presented herein should spur us towards attempting gene therapy which would neutralize steroid receptor gene expressions as a treatment against female genital tract cancers. Meanwhile, various anti-angiogenic inhibitors must be used in progestin-refractory and progestin-dependent tumors.