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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone.
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Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone.

机译:自分泌人类生长激素对人类乳腺癌细胞的表型转化。

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We report here that autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell, including expression of fibronectin and vimentin. Autocrine production of hGH resulted in reduced plakoglobin expression and relocalization of E-cadherin to the cytoplasm, leading to dissolution of cell-cell contacts and decreased cell height. These phenotypic changes were accompanied by an increase in cell motility, elevated activity of specific matrix metalloproteinases, and an acquired ability to invade a reconstituted basement membrane. Forced expression of plakoglobin significantly decreased mammary carcinoma cell migration and invasion stimulated by autocrine hGH. In vivo, autocrine hGH stimulated local invasion of mammary carcinoma cells concomitant with a prominent stromal reaction in comparison with well delineated and capsulated growth of mammary carcinoma cells lackingautocrine production of hGH. Thus, autocrine production of hGH by mammary carcinoma cells is sufficient for generation of an invasive phenotype. Therapeutic targeting of autocrine hGH may provide a mechanistic approach to prevent metastatic extension of human mammary carcinoma.
机译:我们在这里报告,人类生长激素(hGH)的自分泌产生导致乳癌细胞的表型转化,从而它们表现出间充质细胞的形态和分子特征,包括纤连蛋白和波形蛋白的表达。 hGH的自分泌产生导致减少的Plagloglobin表达和E-cadherin重新定位到细胞质,导致细胞间接触溶解并降低细胞高度。这些表型的变化伴随着细胞运动的增加,特定基质金属蛋白酶活性的提高以及获得的入侵重组基底膜的能力。血小板珠蛋白的强迫表达显着降低了自分泌hGH刺激的乳腺癌细胞迁移和侵袭。在体内,与缺乏自分泌的hGH产生的乳腺癌细胞的轮廓分明的和包囊的生长相比,自分泌的hGH刺激了乳腺癌细胞的局部侵袭,并伴有明显的基质反应。因此,由乳腺癌细胞自分泌产生hGH足以产生侵袭性表型。自分泌hGH的治疗目标可能提供一种机制,以防止人类乳腺癌的转移性扩展。

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