Skip to content
Research Article Open access CC BY 4.0

All-Trans Retinoic Acid Downregulates Epidermal Growth Factor Receptor Mediated Regulation of Matrix Metalloproteinase-2 in B16F10 Murine Melanoma Cells

Aniruddha Banerji, Aheli Majumder

Annual Research & Review in Biology · pp. 1–8 · Published 7 Jul 2016

10.9734/ARRB/2016/27388

Abstract

Aims and Study Design: Epidermal growth factor receptor (EGFR) regulates a number of cellular processes, including cell motility, proliferation, differentiation and survival. EGFR mediated signal transduction via mitogen activated protein kinase (MAPK) modulates expression and activity of matrix metalloproteinases (MMPs). Elevated expression and activity of MMP-2 strongly correlates with increased tumour invasiveness. As numerous studies indicate that all-trans retinoic acid (ATRA) has considerable anti-tumorigenic potential, the effect of ATRA on EGFR mediated regulation of MMP-2 via MAPK was studied in this paper using the highly metastatic murine melanoma cell line B16F10 as a model. Methodology: B16F10 cells were cultured in the presence of ATRA (20 μM) for 6, 15 and 24 hrs. EGFR expression and phosphorylation and p38MAPK expression were assayed by Western blot. MMP-2 activity was assayed by gelatin zymography of culture supernatants. MMP-2 and TIMP-2 mRNA expression were assayed by RT-PCR. DNA fragmentation was used to assay the efficacy of ATRA in causing apoptosis. Results: Treatment of B16F10 murine melanoma cells with ATRA (20 µM) for 24 hrs led to an appreciable downregulation of EGFR phosphorylation and expression of EGFR and p38MAPK. Treatment of B16F10 cells with ATRA also inhibited MMP-2 activity and downregulated transcription of MMP-2 while transcription of TIMP-2 was upregulated. Treatment with ATRA did not show appreciable fragmentation of DNA. Conclusion: Downregulation of EGFR expression and phosphorylation and EGFR mediated signal transduction through p38 MAPK could lead to downregulation of MMP-2 transcription. Downregulation of MMP-2 transcription and upregulation of transcription of the MMP inhibitor TIMP-2 could result in loss of MMP-2 activity. Loss of MMP-2 activity would render cells less metastatic. Our findings indicate that treatment with ATRA can inhibit EGFR mediated regulation of MMP-2 activity in B16F10 murine melanoma cells. Such inhibition could have therapeutic potential in clinical management of tumours.

All-trans retinoic acid (ATRA) melanoma epidermal growth factor receptor (EGFR) matrix metalloproteinase-2 (MMP-2) tissue inhibitor of metalloproteinases-2 (TIMP-2) mitogen activated protein kinase (MAPK).

References (24)

  1. 1 Untangling the ErbB signalling network [DOI]
  2. 2 New functions for the matrix metalloproteinases in cancer progression [DOI]
  3. 3 Determination of protein: A modification of the lowry method that gives a linear photometric response [DOI]
  4. 4 Structure and function of matrix metalloproteinases and TIMPs [DOI]
  5. 5 Matrix metalloproteinases and tumor metastasis [DOI]
  6. 6 Review of epidermal growth factor receptor biology [DOI]
  7. 7 Targeting the EGFR signaling pathway in cancer therapy [DOI]
  8. 8 Matrix Metalloproteinases in Human Melanoma [DOI]
  9. 9 Epidermal Growth Factor Receptor Dimerization and Activation Require Ligand-Induced Conformational Changes in the Dimer Interface [DOI]
  10. 10 EGF‐R regulates MMP function in fibroblasts through MAPK and AP‐1 pathways [DOI]
  11. 11 How retinoids regulate breast cancer cell proliferation and apoptosis [DOI]
  12. 12 Suppression of EGF‐induced tumor cell migration and matrix metalloproteinase‐9 expression by capsaicin via the inhibition of EGFR‐mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP‐1 signaling [DOI]
  13. 13 Expression of the epidermal growth factor receptor (EGFR) and the phosphorylated EGFR in invasive breast carcinomas [DOI]
  14. 14 EGFR in melanoma: clinical significance and potential therapeutic target [DOI]
  15. 15 Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine [DOI]
  16. 16 Acute Promyelocytic Leukemia: Recent Advances in Diagnosis and Management [DOI]
  17. 17 All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro [DOI]
  18. 18 Molecular mechanisms of tissue inhibitor of metalloproteinase 2 in the tumor microenvironment [DOI]
  19. 19 Tissue Inhibitor of Matrix Metalloproteinase-2 Regulates Matrix Metalloproteinase-2 Activation by Modulation of Membrane-type 1 Matrix Metalloproteinase Activity in High and Low Invasive Melanoma Cell Lines [DOI]
  20. 20 All-trans retinoic acid (ATRA)-induced apoptosis is preceded by G1 arrest in human MCF-7 breast cancer cells [DOI]
  21. 21 Epithelial growth factor receptor interacting agents [DOI]
  22. 22 Retinoids and Cancer: Antitumoral Effects of ATRA, 9-cis RA and the New Retinoid IIF on the HL-60 Leukemic Cell Line [DOI]
  23. 23 EGF-Receptor Regulation of Matrix Metalloproteinases in Epithelial Ovarian Carcinoma [DOI]
  24. 24 Anti-cancer Potential of All-trans Retinoic Acid (ATRA): A Review [DOI]

Cited by 1

Retinoids as anti-cancer agents and their mechanisms of action.

Ying Jin, S. Teh, H. Lau · American Journal of Cancer Research · 2022

Related research

Article metrics

Real usage data collected on this platform.

83

Page views

0

PDF downloads

15

Outbound clicks

1

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.