The phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathway is commonly deregulated in breast cancer through several mechanisms, including PI3K catalytic subunit alpha (PIK3CA) mutations and loss of phosphatase and tensin homolog (PTEN). The hiperactivated PI3K/AKT signaling can be associated with endocrine or trastuzumab therapy resistance and underscore the impact of targeting the pathway. Our aim was to identify PIK3CA mutations and the mechanisms of PTEN loss and assess their therapeutic consequences in breast cancer patients. In addition, we aimed to identify further possible therapeutic targets associated with PTEN loss. Sixty-nine primary breast cancer samples (24 ER+/PR+/HER2-, 20 HER2+ (ER-/PR-/HER2+) and 25 triple-negative (TN) samples) were studied. We determined the PTEN mRNA levels, PTEN and PIK3CA mutations, PTEN allelic loss and promoter hypermethylation. mRNA expression patterns of PTEN knocked out and wild type MCF10A cell lines were compared using oligonucleotide microarray and their sensitivity to FGFR1 inhibitor PD166866 was tested. Elevated PI3K/AKT pathway activity was found in 68% of TN and about 45% of ER+/PR+ and HER2+ tumors. PTEN loss was dominant in TN and HER2+ tumors, while PTEN loss and PI3K activation were equally represented in ER+/PR+ cancers. The coexistence of PTEN loss and PI3K activation was typical of a portion of HER2+ tumors. The PTEN-deficient MCF10A cell line showed increased expression of certain members of the fibroblast growth factor 2 (FGF2)/FGFR1 pathway. We suppose that loss of PTEN enhances the autocrine FGF signaling promoting cell proliferation. FGF-2 and FGFR1 can be potential targets in PTEN deficient breast cancers.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Johns Hopkins University, Saint Petersburg, FL, USA.
Background: Argonaute2 (Ago2) plays an essential role in RISC-mediated silencing of target mRNAs, which are critical for cellular functions. Argonaute2 Syndrome, also known as Ago2 Syndrome, is a rare neurological disorder recently discovered in humans. It has significant implications for brain development, yet it remains unstudied to date METHOD: To study this effect, we deleted the Ago2 gene in GABAergic (Slc32a1 cre) and Glutamatergic (Slc17a6 cre) mice.
View Article and Find Full Text PDFPotential Contribution of Epithelial Growth Factor Receptor to PI3K/AKT Pathway Dysregulation in Canine Soft Tissue Sarcoma.
In Vivo
December 2024
Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;
Background/aim: Soft tissue sarcoma (STS) is a mesenchymal tumor affecting multiple organs in dogs. Previous studies identified activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB, AKT) pathway in canine STS cell lines and clinical samples, but the underlying mechanism remains unclear. This study investigated PTEN loss, PIK3CA mutation, and EGFR over-expression as potential drivers of PI3K/AKT pathway activation in STS.
View Article and Find Full Text PDFPTEN loss in glioma cell lines leads to increased extracellular vesicle biogenesis and PD-L1 cargo in a PI3K-dependent manner.
J Biol Chem
December 2024
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA. Electronic address:
Phosphatase and Tensin Homologue (PTEN) is one of the most frequently lost tumor suppressors in cancer and the predominant negative regulator of the PI3K/AKT signaling axis. A growing body of evidence has highlighted the loss of PTEN with immuno-modulatory functions including the upregulation of the programmed death ligand-1 (PD-L1), an altered tumor derived secretome that drives an immunosuppressive tumor immune microenvironment (TIME), and resistance to certain immunotherapies. Given their roles in immunosuppression and tumor growth, we examined whether the loss of PTEN would impact the biogenesis, cargo, and function of extracellular vesicles (EVs) in the context of the anti-tumor associated cytokine interferon-γ (IFN-γ).
View Article and Find Full Text PDFBiochemical Mechanisms and Rehabilitation Strategies in Osteoporosis-Related Pain: A Systematic Review.
Clin Pract
December 2024
Department of Experimental Medicine (Di.Me.S), University of Salento, 73100 Lecce, Italy.
Article Synopsis
- Osteoporosis leads to significant bone mass loss, contributing to acute and chronic pain, necessitating a deeper understanding of its biochemical and neurophysiological mechanisms.
- A systematic review of studies from 2018 to 2024 revealed key findings on the miR-92a-3p/PTEN/AKT pathway and the importance of muscle-bone interactions, emphasizing mechanotransduction for bone health.
- Effective pain management strategies identified include physical therapies, cognitive behavioral therapy, and pharmacological options, highlighting the potential for integrated treatment approaches to improve pain relief and functional outcomes for patients.
Exosomes derived from hypoxic mesenchymal stem cells restore ovarian function by enhancing angiogenesis.
Stem Cell Res Ther
December 2024
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, P.R. China.
Background: hucMSC-exosomes can be engineered to strengthen their therapeutic potential, and the present study aimed to explore whether hypoxic preconditioning can enhance the angiogenic potential of hucMSC-exosomes in an experimental model of POF.
Methods: Primary hucMSCs and ROMECs were isolated from fresh tissue samples and assessed through a series of experiments. Exosomes were isolated from hucMSCs under normoxic or hypoxic conditions (norm-Exos and hypo-Exos, respectively) and then characterized using classic experimental methods.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!