Related Experiment Video
Updated: Jan 18, 2026
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Hsp90α as a promising therapeutic target for suppressing tumor progression in Lactotroph PitNETs
Jie Wu1, Zhengan Zhou1, Chongxue Ding1
1Department of Neurosurgery, The first Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
Background:
Aggressive Lactotroph Pituitary Neuroendocrine Tumors (Lactotroph PitNETs) usually exhibit invasive growth behavior and resistance to dopamine agonists, showing difficulty in radical treatment and a high recurrence rate. Heat shock protein 90α(Hsp90α),a pivotal isoform of the heat shock protein 90(Hsp90) family, acts as a central chaperone that stabilizes numerous oncoproteins driving tumor progression, but its role in Lactotroph PitNETs remains unclear.
Objective:
To study the effect of Hsp90α knockdown on the proliferation and invasiveness of Lactotroph PitNETs cells (MMQ).
Methods:
Hsp90α and EGFR expression was compared between 18 aggressive and 22 Non-Aggressive human Lactotroph PitNETs by IHC and immunofluorescence. MMQ rat lactosomatotroph cells were transduced with lentiviral shRNA targeting Hsp90α(shHsp90α). Cell proliferation (CCK8),apoptosis (Annexin-V/7-AAD flow cytometry), Prolactin (PRL) secretion (ELISA), migration and invasion (Transwell) were assessed. Western blotting evaluated EGFR,PRL,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR.
Results:
Aggressive Lactotroph PitNETs displayed higher Hsp90α and EGFR expression and showed a notable degree of spatial overlap. Hsp90α knockdown reduced EGFR,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR levels, decreased proliferation, increased apoptosis, lowered PRL secretion, and impaired migration and invasion.
Conclusions:
Hsp90α knockdown simultaneously destabilizes EGFR and its downstream AKT/mTOR and ERK axes, resulting in multi-modal suppression of Lactotroph PitNETs invasion. Targeting Hsp90α may offer a novel therapeutic strategy for Aggressive Lactotroph PitNETs refractory to standard medical therapy.
Insights
Targeting heat shock protein 90 alpha (Hsp90α) in aggressive Lactotroph Pituitary Neuroendocrine Tumors (PitNETs) reduces cell proliferation and invasion. Hsp90α knockdown destabilizes EGFR and its downstream pathways, offering a potential new therapy for resistant tumors.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Aggressive Lactotroph Pituitary Neuroendocrine Tumors (PitNETs) are challenging to treat due to invasive growth and resistance to dopamine agonists.
- Heat shock protein 90 alpha (Hsp90α) is a chaperone protein involved in tumor progression, but its role in Lactotroph PitNETs is not well understood.
Purpose of the Study:
- To investigate the effect of Hsp90α knockdown on the proliferation and invasiveness of Lactotroph PitNETs cells.
- To explore the molecular mechanisms underlying Hsp90α's role in Lactotroph PitNETs.
Main Methods:
- Compared Hsp90α and EGFR expression in aggressive versus non-aggressive human Lactotroph PitNETs.
- Utilized lentiviral shRNA to knock down Hsp90α in MMQ cells.
- Assessed cell proliferation, apoptosis, Prolactin secretion, migration, and invasion.
- Analyzed key signaling proteins including EGFR, AKT, ERK1/2, and mTOR via Western blotting.
Main Results:
- Aggressive Lactotroph PitNETs showed higher Hsp90α and EGFR expression.
- Hsp90α knockdown decreased proliferation, increased apoptosis, and reduced Prolactin secretion.
- Knockdown of Hsp90α led to reduced levels of EGFR and its downstream signaling molecules (AKT, mTOR, ERK1/2).
- Impaired migration and invasion capabilities were observed following Hsp90α knockdown.
Conclusions:
- Hsp90α knockdown destabilizes EGFR and its downstream AKT/mTOR and ERK pathways.
- This multi-modal suppression effectively reduces Lactotroph PitNETs invasion.
- Targeting Hsp90α presents a promising therapeutic strategy for aggressive Lactotroph PitNETs resistant to current treatments.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:23Abnormal Proliferation