Abstract 5939
Background
Matrix metalloproteinases (MMPs) specifically hydrolyze the extracellular matrix proteins. MMPs are inhibited by tissue inhibitors of MMPs (TIMPs). Changes in the expression levels of MMPs and TIMPs have been described in various cancers, including breast cancer (BC).
Methods
We analyzed methylation status of 11 MMP genes (MMP2, MMP11, MMP14, MMP15, MMP16, MMP17, MMP21, MMP23B, MMP24, MMP25, MMP28) and 4 TIMP genes (TIMP1, TIMP2, TIMP3, TIMP4) in 183 BC samples and 183 matched samples of morphologically normal adjacent tissues, 6 BC cell lines (ZR711, HBL100, HS578T, BT474, T47D, MCF7), and 6 autopsy samples of normal breast tissues by methylation sensitive restriction enzyme digestion PCR (MSRE-PCR).
Results
In our collection of BC samples, cancer related abnormal methylation was observed for the MMP2, MMP23B, MMP24, MMP25, and MMP28 genes of the MMPs family (Table). Other MMP genes under study were nonmethylated both in tumors and in normal tissues, as well as the TIMP genes TIMP2 and TIMP3. The promoter regions of TIMP1, TIMP4, MMP14, and MMP21 were found to be constitutively methylated in breast tissues, no matter cancerous or normal. A multiple correspondence analysis demonstrated that nonmethylated status of the promoter regions of MMP2, MMP23B, MMP24, MMP25, MMP28 is associated with lack of HER2 expression. The methylated status of the MMP23B is associated with a higher level (3+) of HER2 expression. Table: MMP genes differentially methylated in BC.Table:
20P MMP genes differentially methylated in BC
Gene | Methylated in BC, % | Methylated in normal breast tissues | Presence (+) or absence (–) of methylation in BC cell lines | |||||
---|---|---|---|---|---|---|---|---|
ZR751 | MCF7 | T47D | BT474 | HBL100 | HS578T | |||
MMP2 | 7,7 (14/183) | 0 | + | + | + | - | - | - |
MMP23B | 17 (31/182) | 0 | + | + | + | - | + | + |
MMP24 | 11,9 (20/168) | 0 | - | - | - | + | + | - |
MMP25 | 15,4 (28/182) | 0 | - | + | + | - | + | - |
MMP28 | 4,9 (9/183) | 0 | + | + | + | + | + | - |
Conclusions
Taken that HER2-positive BC is a more aggressive disease, one can assume that unsuppressed expression of the MMP2, MMP23B, MMP24, MMP25, MMP28 genes allowed by the absence of abnormal methylation of their promoters is characteristic for less aggressive BCs. Legal entity responsible for the study: Research Centre for Medical Genetics. Funding: The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Research Centre for Medical Genetics.
Funding
Ministry of Science and Higher Education of the Russian Federation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3371 - Pulmonary Resectable Metastases of Osteosarcoma With Apatinib and CHemotherapy (PROACH):A Multi-Center Phase II Randomized Clinical Trial
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
1666 - National Clinical-biological Prospective Cohort of Incident Cases of Aggressive Fibromatosis, AF (ALTITUDES)
Presenter: Thomas Ryckewaert
Session: Poster Display session 1
Resources:
Abstract
5531 - Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy: The HOLISTIC study
Presenter: Eugenie Younger
Session: Poster Display session 1
Resources:
Abstract
5568 - Assessing QUality of life and Experiences of diagnostic Trajectories of Sarcoma patients: The QUEST study protocol
Presenter: Vicky Soomers
Session: Poster Display session 1
Resources:
Abstract