ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 23 citations in OpenAlex.
- Autophagy in Ovarian Cancer, an Opportunity or an Additional Threat?International journal of molecular sciences · 2026Review
- The Roles of MicroRNAs, Oncogenes, and Tumor Suppressor Gene Molecular Subtypes of Breast Cancer: Therapeutic Potential of Pharmaceutical and Natural Products.International journal of breast cancer · 2026Review
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.International journal of nanomedicine · 2024Review
- Drug-resistant HER2-positive breast cancer: Molecular mechanisms and overcoming strategies.Frontiers in pharmacology · 2022Review
- Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents.Oncology letters · 2019Article
- Cathepsin B: A sellsword of cancer progression.Cancer letters · 2019Review
- Sevoflurane post-conditioning alleviates neonatal rat hypoxic-ischemic cerebral injury via Ezh2-regulated autophagy.Drug design, development and therapy · 2019Article
- Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K/Akt pathway.Journal of cellular and molecular medicine · 2018Article
- Livin participates in resistance to trastuzumab therapy for breast cancer through ERK1/2 and AKT pathways and promotes EMT-like phenotype.RSC advances · 2018Article
- Linking Autophagy and the Dysregulated NFκB/ SNAIL/YY1/RKIP/PTEN Loop in Cancer: Therapeutic Implications.Critical reviews in oncogenesis · 2018Review
- Protein Kinase Targets in Breast Cancer.International journal of molecular sciences · 2017Review
- Autophagy in UV Damage Response.Photochemistry and photobiology · 2017Review
- PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.PloS one · 2017Article
- Article
- Insights into APC/C: from cellular function to diseases and therapeutics.Cell division · 2016Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.
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