A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis
A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis
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DOI：
10.1667/0033-7587(2001)155
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发表时间：
2001-01-01
影响因子：
3.4
通讯作者：
Trosko, JE
中科院分区：
文献类型：
--
作者：
Chang, CC;Sun, W;Trosko, JE
两种类型的人乳腺上皮细胞（HBEC）的特点。与表达基底上皮细胞表型的II型HBEC相反，I型HBEC缺乏间隙连接细胞间通讯，并且能够非贴壁依赖性生长和表达管腔上皮细胞标志物、雌激素受体和干细胞特征（即分化成其他细胞类型和在基质胶上形成出芽/导管类器官的能力）。这两种类型的细胞的比较研究揭示了I型HBEC对SV 40大T抗原永生化的高敏感性，尽管两种类型的细胞在用SV 40转染后同样能够获得延长的寿命（绕过衰老）。永生化伴随着中期传代后亲本细胞中低水平端粒酶活性的升高（类似于60个累积群体倍增水平）。因此，HBEC确实具有低水平的端粒酶活性，并且具有干细胞特征的I型HBEC更容易受到端粒酶激活和永生化的影响，这一机制可能使它们有资格作为乳腺癌发生的靶细胞。通过用X射线（2戈伊x 2）进一步处理并用突变的ERBB 2（也称为NEU）癌基因转染，导致酪氨酸磷酸化的p185（ERBB 2）的表达，永生化的I型HBEC可转化为高度致瘤性细胞，（C）2001，Radiation Research Society。
Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage (similar to 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated, (C) 2001 by Radiation Research Society.