Human chorionic gonadotropin (hCG) prevents the transformed phenotypes induced by 17 beta-estradiol in human breast epithelial cells.
Human chorionic gonadotropin (hCG) prevents the transformed phenotypes induced by 17 beta-estradiol in human breast epithelial cells.
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DOI：
10.1016/j.cellbi.2009.07.002
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发表时间：
2009-11
影响因子：
3.9
通讯作者：
Fernandez, Sandra V.
中科院分区：
文献类型：
--
作者：
Kocdor, Hilal;Kocdor, Mehmet A.;Russo, Jose;Snider, Kara E.;Vanegas, Johana E.;Russo, Irma H.;Fernandez, Sandra V.
人绒毛膜促性腺激素（hCG）是怀孕期间产生的一种激素，可通过乳腺上皮的分化引起终生的癌难性。人乳腺上皮细胞MCF-10F在胶原蛋白中形成小管，模仿正常的小管，我们已经证明17 β-雌二醇（E2）改变了这些细胞的小管形成模式。体外观察重组人绒毛膜促性腺激素（rhCG）对E2诱导MCF-10F转化的影响。MCF-10F细胞分别用70nM E2单独或联合50 IU/ml rhCG处理2周，对照组用DMSO（溶解E2的溶剂）或单独rhCG处理2周。处理结束后，将细胞镀于I型胶原基质（3d培养）中，检测细胞转化的2种主要表型，即导管生成能力的丧失和固体团块的形成。虽然E2显著增加了固体团块的形成，但当E2与rhCG联合处理MCF-10F细胞时，这种作用被阻止。此外，E2增加了主导管宽度（p<0.001），并导致管腔结构的破坏，而rhCG增加了小管的长度（p<0.001）并产生了三级分支。综上所述，rhCG能够消除雌二醇的转化能力，并通过增加乳腺上皮细胞在胶原中形成的小管分支而具有分化特性。这些结果进一步支持了我们的假设，即乳腺癌预防的终端分化假设，该假设预测hCG治疗通过向难治性干细胞2分化而导致易感干细胞1的损失，从而使乳腺的分化增加，从而保护乳腺免受致瘤性变化。
Human chorionic gonadotropin (hCG), a hormone produced during pregnancy, can elicit life-long refractoriness to carcinogenesis by differentiation of the breast epithelium. Human breast epithelial cells MCF-10F form tubules in collagen, mimicking the normal ductules, We have shown that 17 β-estradiol (E2) alter the ductulogenic pattern of these cells. The effect of the recombinant hCG (rhCG) in vitro was evaluated on the transformation of MCF-10F induced by E2. MCF-10F cells were treated with 70nM E2 alone or in combination with 50 IU/ml rhCG during 2 weeks, while the controls were treated with DMSO (the solvent in which E2 was dissolved) or rhCG alone. At the end of treatment, the cells were plated in type I collagen matrix (3D-cultures) for detecting 2 main phenotypes of cell transformation, namely the loss of ductulogenic capacity and the formation of solid masses. Although E2 significantly increased solid mass formation, this effect was prevented when MCF-10F cells were treated with E2 in combination with rhCG. Furthermore, E2 increased the main duct width (p<0.001), and caused a disruption of the luminal architecture, whereas rhCG increased the length of the tubules (p<0.001) and produced tertiary branching. In conclusion, rhCG was able to abrogate the transforming abilities of estradiol, and had the differentiating property by increasing the branching of the tubules formed by breast epithelial cells in collagen. These results further support our hypothesis, known as the terminal differentiation hypothesis of breast cancer prevention, that predicts that hCG treatment results in protection from tumorigenic changes by the loss of susceptible stem cells 1 through a differentiation to refractory stem cells 2 and increase differentiation of the mammary gland.
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