Hosobuchi M, Stampfer M R
Lawrence Berkeley Laboratory, Cell and Molecular Biology Division, Berkeley, California 94720.
In Vitro Cell Dev Biol. 1989 Aug;25(8):705-13. doi: 10.1007/BF02623723.
Normal human mammary epithelial cells (HMEC) from different individual reduction mammoplasty specimens were all growth inhibited, and showed a flattened, elongated morphology in response to human recombinant transforming growth factor beta 1 (TGF beta). The degree of growth inhibition varied among specimens, but none of the normal HMEC maintained growth in the continued presence of TGF beta. The degree of growth inhibition also varied with cell age in vitro, cells closer to senescence being more sensitive. TGF beta sensitivity was additionally assayed in two established cell lines derived from one of the reduction mammoplasty specimens after exposure to benzo(a)pyrene. Although varying degrees of growth inhibition and morphologic changes were observed in the cell lines, both lines contained populations that maintained active growth in the presence of TGF beta. Subclones of these lines demonstrated a great plasticity in their growth response to TGF beta, with individual clones ranging from strongly growth inhibited to nearly unaffected. These results suggest that multiple factors influence the extent of TGF beta-induced growth effects on both normal and transformed mammary epithelial cells, and that some of these factors may act through epigenetic mechanisms.
来自不同个体的缩乳术标本的正常人类乳腺上皮细胞（HMEC）均受到生长抑制，并且在人重组转化生长因子β1（TGF-β）作用下呈现扁平、细长的形态。不同标本间生长抑制程度各异，但在持续存在TGF-β的情况下，没有正常HMEC能维持生长。生长抑制程度也随体外细胞年龄而变化，越接近衰老的细胞越敏感。在暴露于苯并(a)芘后，从其中一个缩乳术标本衍生的两个已建立细胞系中额外检测了TGF-β敏感性。尽管在细胞系中观察到不同程度的生长抑制和形态变化，但两个细胞系中均有在TGF-β存在下维持活跃生长的细胞群体。这些细胞系的亚克隆在对TGF-β的生长反应中表现出很大的可塑性，单个克隆的生长抑制程度从强烈抑制到几乎不受影响不等。这些结果表明，多种因素影响TGF-β对正常和转化乳腺上皮细胞诱导的生长效应程度，并且其中一些因素可能通过表观遗传机制起作用。
