Direct action of estrogen on sequence of progression of human preneoplastic breast disease.
Direct action of estrogen on sequence of progression of human preneoplastic breast disease.
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发表时间：
1998-05
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通讯作者：
M. Shekhar;P. Nangia-Makker;S. R. Wolman;Larry Tait;Gloria H. Heppner;Daniel W. Visscher
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作者：
M. Shekhar;P. Nangia-Makker;S. R. Wolman;Larry Tait;Gloria H. Heppner;Daniel W. Visscher
我们使用MCF10AT人类增殖性乳腺疾病异种移植模型来检查雌二醇暴露对肿瘤前病变形态学进展的早期影响，并确定雌激素在形态学序列中可能起作用的步骤。雌二醇对原位位置雌激素受体阳性MCF10AT细胞肿瘤进展的影响在切除卵巢的雌性裸鼠中进行了研究，这些裸鼠皮下植入了17 -雌二醇或安慰剂颗粒。10周时，对雌激素补充组病变的组织学分析显示，92%的病变表现为不典型增生、原位癌或浸润性癌的组织学特征，其余8%表现为中度增生的组织学特征。这些高度增生的病变与对照组形成鲜明对比，对照组中60%的样本没有显示增生的证据。与对照异种移植物相比，雌激素暴露的异种移植物表现出广泛的乳头状生长区域、腺样病变区域、明显的宿主炎症浸润和血管生成。我们的研究结果表明，雌激素对良性或癌前导管上皮具有促进生长的作用：1)病变形成的频率，2)病变的大小，3)从正常/轻度增生向非典型增生转变的速度，4)不典型增生的程度，5)血管生成。
We have used the MCF10AT xenograft model of human proliferative breast disease to examine the early effects of estradiol exposure on morphological progression of preneoplastic lesions and to define the step(s) in the morphological sequence at which estrogen may act. The effects of estradiol on neoplastic progression of estrogen-receptor-positive MCF10AT cells in the orthotopic site were examined in ovariectomized female nude mice that received subcutaneous administration of implants of 17beta-estradiol or placebo pellets. At 10 weeks, histological analysis of the lesions derived from the estrogen-supplemented group revealed that 92% of lesions displayed histological features of atypical hyperplasia, carcinoma in situ, or invasive carcinoma, and the remaining 8% exhibited histological features of moderate hyperplasia. These highly proliferative lesions are in marked contrast to the control group in which 60% of samples displayed no evidence of hyperplasia. In contrast with control xenografts, estrogen-exposed xenografts demonstrated extensive areas of papillary growth, adenosis-like areas, prominent host inflammatory infiltration, and angiogenesis. Our results suggest that estrogen exerts a growth-promoting effect on benign or premalignant ductal epithelium by enhancing 1) the frequency of lesion formation, 2) the size of lesions, 3) the speed of transformation from normal/mild hyperplasia to those with atypia, 4) the degree of dysplasia, and 5) angiogenesis.