Study of endocrinological contribution for invasion and metastasis in gynecological cancers

孕酮非依赖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。在女性生殖道癌的进展过程中，雌激素受体第5外显子剪接变异体(ER E5SV)作为转录激活因子相对过表达，孕激素受体A型(PR-A)作为转录抑制因子表达受损，可能与肿瘤的转移有关。此外，雌激素可能促进某些子宫内膜癌的多个阶段的侵袭和转移，而孕激素可以抑制雌激素相关的事件，特别是肿瘤血管生成。肿瘤生长对孕激素的异常反应可能与PR-A表达受损有关。孕激素受体B(PR-B)优势表达而无PR-A转录抑制的状态与某些肿瘤的发生有关，另一方面，孕激素是否对PR突变的女性生殖道癌的肿瘤血管生成有影响尚不清楚。最有可能的是，孕激素作为一种抗血管生成疗法，在PR突变的肿瘤中效果较差。这里提供的数据应该会促使我们尝试基因疗法，这种疗法将中和类固醇受体基因的表达，作为治疗女性生殖道癌的方法。同时，对于孕激素不耐药和孕激素依赖的肿瘤，必须使用各种抗血管生成抑制剂。

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.