Premium
Over‐expression of cyclin D1 induces glioma invasion by increasing matrix metalloproteinase activity and cell motility
Author(s) -
AratoOhshima Teruyo,
Sawa Hiroki
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991029)83:3<387::aid-ijc15>3.0.co;2-o
Subject(s) - cyclin d1 , motility , matrix metalloproteinase , cancer research , biology , extracellular matrix , cyclin d , cell migration , microbiology and biotechnology , cell , cell cycle , biochemistry
In order to define the role of cyclin D1 in the progression of malignant glioma, cells over‐expressing cyclin D1 were constructed (a‐1 cells). They exhibited significantly increased invasiveness as compared with mock‐transfected cells. Since cellular invasion is thought to depend on extracellular‐matrix degradation, we determined whether cyclin‐D1 expression modifies the activity of matrix metalloproteinases (MMPs). Increased gelatinolytic activity of latent type MMP‐2 (proMMP‐2) and active MMP‐2 was observed in a‐1 cells. Moreover, cyclin‐D1 expression was associated with increased activation of proMMP‐9 through MMP‐3. Wound assays showed an increase of cell motility in a‐1 cells. Cyclin‐D1 expression was found to be associated with up‐regulation of Rac1, which modulates the formation of ruffling membranes and cell motility. Our results show that cyclin D1 may modulate invasive ability by increasing MMP activity and cell motility, and suggests a novel function of cyclin D1 in the progression of malignant gliomas. Int. J. Cancer 83:387–392, 1999. © 1999 Wiley‐Liss, Inc.