MMP-7 is involved in the aging of primary human mammary epithelial cells (HMEC)
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- 作者：Catharina Bertram ; Ralf Hass
- 关键词：Aging ; Mammary epithelial cells ; HMEC ; Breast cancer ; Matrix metalloproteinase ; Senescence
- 刊名：Experimental Gerontology
- 出版年：2008
- 出版时间：March 2008
- 年：2008
- 卷：43
- 期：3
- 页码：209-217
- 全文大小：718 K
文摘
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 β-galactosidase as aging marker, the cells restructured their attachment, increased in size and ceased to divide. Young HMEC until P11 demonstrated a nearly 100 % expression of distinct adhesion molecules such as CD24, integrin β1 (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 P11 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 G2/M cell cycle arrest and a 2- to 3-fold enhanced senescence-associated β-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.