经典的子宫内膜样腺癌（内膜癌）雌激素致瘤理论既不能解释在无孕激素拮抗的雌激素刺激下绝大多数绝经后妇女不会发生内膜癌，亦不能解释少数育龄妇女虽然有周期性孕激素分泌，却依然出现内膜细胞的恶性转化。我们前期研究表明，内膜癌局部存在原位雌激素合成：内膜癌细胞分泌的白细胞介素6能刺激间质细胞产生能转化雄激素为雌激素的芳香化酶。课题组预实验结果表明：（1）间质细胞合成的Activin A可以上调内膜癌细胞芳香化酶的表达；（2）TNF-α介导内膜癌细胞Activin A的分泌。本项研究旨在证明内膜癌细胞产生的TNF-α能促进间质细胞分泌Activin A、Activin A进而调控内膜癌细胞合成芳香化酶、芳香化酶导致的原位雌激素合成又促使癌细胞分泌TNF-α的假想。如能证实以上，不仅能为内膜癌雌激素致癌理论提供重要的补充，而且能为寻找基于阻止雌激素原位合成导致的内膜癌细胞增殖的靶向治疗开辟一条新的途径。

Classic endometrioid adenocarcinoma estrogen theory of carcinogensis does not explain the phenomenon that endometrial carcinoma does not occur in most postmenopausal women in the absence of progesterone antagonist of estrogen, and also cannot explain the malignant transformation in minority of women of childbearing age despite of the periodic progesterone secretion. Our previous study showed the existence of estrogen in situ biosynthesis: Interleukin 6 secretion from endometrial cancer cells can stimulate aromatase expression in stomal cells which can transform androgen into estrogen. Our pre-experiment results show that: (1) Activin A synthesis in intratumoral stomal cells stimulates aromatase expressin in cancer cells; (2) tumor necrosis factor alpha (TNF-α) mediates the secretion of Activin A. We will design the corresponding experiment, in ordor to prove the hypothesis that TNF- α produced in endometrial cancer cells promotes stomal cells secretion of Activin A, which stimulates aromatase expression, leading to in situ estrogen synthesis in cancer cells, and estrogen in turn increases TNF-α secretion. Once the hypothesis is confirmed, not only can we provide an important supplement theory of estrogen carcinogenesis in endometrial carcinoma, but also look for a new target for blocking estrogen synthesis in situ.