Phosphatidylinositol 3′ Kinase (PI3K), A Crucial Regulator of Epidermal Growth Factor Receptor (EGFR) Modulated MMP-2, MMP-9 and MT1-MMP Expression in Breast Cancer Cells

Phosphatidylinositol 3′ Kinase (PI3K), A Crucial Regulator of Epidermal Growth Factor Receptor (EGFR) Modulated MMP-2, MMP-9 and MT1-MMP Expression in Breast Cancer Cells

In breast cancer, tumour metastasis is responsible for the majority of mortality. Breast cancers with elevated epidermal growth factor receptor (EGFR) activity have been identified with increased tumour invasion and poorer prognosis. Increased expression of MMP-2, MMP-9 and MT1-MMP matrix metalloproteinases ( MMPs) indicates a strong association with increased metastasis and poorer survival in patients with breast cancer. The role of phosphatidylinositol 3 ‘kinase (PI3 K) in EGFR-mediated control of MMPs in breast cancer was investigated in our current research, using the invasive human breast adenocarcinoma cell line MDA-MB-231 as a model. Upon EGFR interaction with its cognate ligand EGF, PI3 K phosphorylation is increased. EGFR modulated upregulation of MMP-2, MMP-9 and MT1-MMP for both protein and mRNA is impeded by inhibition of PI3 K with the PI3 K inhibitor LY294002. Niveaus. In this way, PI3 K appears to be crucially involved in EGFR mediated signalling cascades promoting elevated expression of MMP-2, MMP-9 and MT1-MMP in MDA-MB-231 cells. Our findings explain the significance of PI3 K mediated signalling in modulating invasive potential in breast cancer cells upon EGFR activation by controlling the expression of MMP-2, MMP-9 and MT1-MMP in breast cancer cells and indicate that the use of PI3 K inhibitors may have therapeutic utility in inhibiting tumour invasion (improving patient survival) in breast cancers with high and aberrant EGFR activity.

Author (s) Details

Ms. Aheli Majumder
Post Graduate Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata, 30 Mother Teresa Sarani, Kolkata 700016, West Bengal, India.

Dr. Sajal Ray
Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, West Bengal, India.

Dr. Aniruddha Banerji
Post Graduate Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata, 30 Mother Teresa Sarani, Kolkata 700016, West Bengal, India.

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