| Title |
Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy
|
|---|---|
| Published in |
Tumor Biology, November 2015
|
| DOI | 10.1007/s13277-015-4392-0 |
| Pubmed ID | |
| Authors |
Liao Ning, Zhang Guo-Chun, An Sheng-Li, Li Xue-Rui, Wang Kun, Zu Jian, Ren Chong-Yang, Wen Ling-Zhu, Lv Hai-Tong |
| 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 27 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 15% |
| Student > Doctoral Student | 4 | 15% |
| Student > Postgraduate | 3 | 11% |
| Student > Ph. D. Student | 2 | 7% |
| Researcher | 2 | 7% |
| Other | 4 | 15% |
| Unknown | 8 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 22% |
| Medicine and Dentistry | 5 | 19% |
| Agricultural and Biological Sciences | 4 | 15% |
| Social Sciences | 2 | 7% |
| Economics, Econometrics and Finance | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 November 2015.
All research outputs
#19,054,237
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Outputs from Tumor Biology
#1,389
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#204,957
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Outputs of similar age from Tumor Biology
#123
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