The role of PTEN on breast cancer
Keywords:
PTEN, Breast Cancer, Cell cycle, trastuzumabAbstract
Phosphatase and tensin homolog on chromosome 10 (PTEN) are tumor suppressors with phosphatase activity against phospholipids and proteins. The tumor suppressor activity of PTEN is attributed to its lipid phosphatase activity against PI (3,4,5) P3 (PIP3). The PIP3 is the phospholipid product of phosphoinositide-3-kinase (PI3K), the crucial signal transduction pathway.The PTEN is the essential negative regulator of PI3K and AKT pathway.The PTEN dephosphorylates PIP3 to PIP2, PTEN reverses the action of PI3K. PTEN plays significant roles in regulating biological processes, including growth, adhesion, migration, invasion, apoptosis, cancer, and other diseases. Therefore, level and function of PTEN are tightly regulated at transcription, post-transcription, and post-translation levels. Protein-protein interactions and their locations also regulate PTEN. Besides a tumor suppressor, PTEN is also a guardian of the genome frequently mutated and deleted in human cancer, including breast cancer. PTEN deficiency disrupts the fundamental processes of genetic transmission. Cells lacking PTEN have cell cycle deregulation and cell fate reprogramming. Breast cancer patients with PTEN loss had significantly poorer responses to trastuzumab-base therapy than those with normal PTEN. Thus PTEN loss is a powerful predictor of trastuzumab resistance. In addition, that PI3K-targeting therapies rescued PTEN loss-induced trastuzumab resistance. The understanding of the biological role of PTEN, the PTEN expression and activity are regulated, and PTEN dysregulation in human cancer, including breast cancer, could provide new strategies for cancer therapies.
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