MMP-7 is involved in the aging of primary human mammary epithelial cells (HMEC)
MMP-7 is involved in the aging of primary human mammary epithelial cells (HMEC)
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DOI：
10.1016/j.exger.2007.11.007
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发表时间：
2008-03-01
影响因子：
3.9
通讯作者：
Hass, Ralf
中科院分区：
文献类型：
--
作者：
Bertram, Catharina;Hass, Ralf
原代培养的人乳腺上皮细胞在第12代（P12）和第16代（P16）之间的老化过程中发生了显著的形态和功能变化。伴随着衰老相关的P-半乳糖苷酶作为衰老标志物的进行性和显著表达，细胞重建了它们的附着，大小增加并停止分裂。直到P11的年轻HMEC显示出与人乳腺肿瘤细胞系MCF-7相似的不同粘附分子如CD 24、整联蛋白β 1（CD 29）和CD 44的几乎100%表达。与衰老相关的细胞粘附变化平行，衰老的P16 HMEC中CD 24和CD 44的表达下降。然而，CD 29的水平在老化过程中保持不变。在致瘤MCF-7细胞中表达至约100%的肿瘤相关Muc-1（CD 227）在P11的年轻HMEC中可检测到51%，在P16的老年HMEC中下降至37%。与细胞形状的重塑，不同的基质金属蛋白酶，包括MMP-7的表达水平显着下降，在老化的HMEC。相比之下，MMP-1、MMP-2和MMP-9保持不变，表明MMP-7在HMEC老化过程中可能的功能作用。事实上，通过RNAi下调MMP-7显示，与对照siRNA转染子和对照HMEC相比，G（2）/M细胞周期阻滞显著升高，衰老相关的β-半乳糖苷酶表达增加2- 3倍。总之，这些发现表明MMP-7表达的降低有助于人类乳腺上皮细胞的加速老化。(c)2008年由Elsevier Inc.出版
Primary cultures of human mammary epithelial cells underwent significant morphological and functional changes during the aging process between passage 12 (P12) and passage 16 (P16). Concomitant with a progressive and significant expression of senescence-associated P-galactosidase as aging marker, the cells restructured their attachment, increased in size and ceased to divide. Young HMEC until P I I demonstrated a nearly 100% expression of distinct adhesion molecules such as CD24, integrin beta 1 (CD29) and CD44 similar to the human mammary tumor cell line MCF-7. In parallel with the aging-associated alterations of the cell adhesion, expression of CD24 and CD44 dropped in senescent P16 HMECs. However, levels of CD29 remained unchanged during the aging process. The tumor-associated Muc-1 (CD227), which was expressed to about 100% in the tumorigenic MCF-7 cells, was detectable in 51% of young HMEC in PI I and declined to 37% in aged HMEC in P16. In association with the remodeling of cell shape, expression levels of distinct matrix metalloproteinases including MMP-7 markedly decreased in aging HMEC. In contrast, MMP-1, MMP-2 and MMP-9 remained unchanged indicating a possible functional role of MMP-7 during the HMEC aging process. Indeed, down-modulation of MMP-7 by RNAi revealed a significantly elevated G(2)/M cell cycle arrest and a 2- to 3-fold enhanced senescence-associated P-galactosidase expression as compared to control siRNA transfectants and control HMEC, respectively. Together, these findings suggested that decreasing MMP-7 expression contributes to accelerated aging of human mammary epithelial cells. (c) 2008 Published by Elsevier Inc.