MMP-7 is involved in the aging of primary human mammary epithelial cells (HMEC).
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 beta-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 beta1 (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 G(2)/M cell cycle arrest and a 2- to 3-fold enhanced senescence-associated beta-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.
Bertram
Catharina
C
Department of Gynecology (OE6411), Medical School Hannover, Carl-Neuberg-Str 1, Hannover, Germany.
Hass
Ralf
R
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7