title: MMP-7 is involved in the aging of primary human mammary epithelial cells (HMEC).
abstract: 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.
authors.affiliation: Department of Gynecology (OE6411), Medical School Hannover, Carl-Neuberg-Str 1, Hannover, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Bertram
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
mesh_terms: 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
chemical_list: D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7