MDM2 and PSMA play inhibitory roles in metastatic breast cancer cells through regulation of matrix metalloproteinases

Bradbury, Robyn, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 and Cui, Yuxin 2016. MDM2 and PSMA play inhibitory roles in metastatic breast cancer cells through regulation of matrix metalloproteinases. Anticancer Research 36 , pp. 1143-1152.

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Abstract

Mouse double minute 2 (MDM2) and prostate-specific membrane antigen (PSMA) are currently under investigation as individual therapeutic targets due to their overexpression in many cancer types, as well as their pro-tumorigenic effect on cells. Recently, knockdown of PSMA was linked to a decrease in MDM2 and matrix metalloproteinase 2 (MMP2) and an increase in MMP3 and MMP13 expression. We aimed to assess the link between PSMA, MDM2 and the MMPs in metastatic breast cancer cell lines. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (PCR) and western blotting were used to assess siRNA-mediated knockdown of MDM2 and PSMA in MDA-MB-231 and ZR-75.1 breast cancer cells. Assays to assess the growth, adhesion, migration and invasion of the cells following siRNA treatment were undertaken. MMP and tissue inhibitor of matrix metalloproteinases (TIMP) levels were assessed via quantitative PCR. RESULTS: Knockdown of MDM2 resulted in a decrease in PSMA expression levels and vice versa; although this trend was not replicated at the protein level. Knockdown of each of the molecules resulted in a decrease in growth, adhesion, migration and invasive ability of breast cancer cells. Both knockdowns led to a decrease in MMP2 and an increase in MMP3, -10 and -13 gene expression. CONCLUSION: MDM2 and PSMA may co-regulate the expression of certain MMPs and, thus, the functionality of cells in metastatic breast cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	MDM2; MMPs; PSMA; breast cancer; matrix metalloproteinases
Publisher:	International Institute of Anticancer Research
ISSN:	0250-7005
Funders:	Cancer Research Wales
Date of First Compliant Deposit:	9 April 2016
Date of Acceptance:	14 February 2016
Last Modified:	01 Nov 2022 09:44
URI:	https://orca.cardiff.ac.uk/id/eprint/89022

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