RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo

Autor: Yuan-Yuan Cheng, Jia-Wen Xu, Jing-Da Xu, Xiuping Liu, Zu-De Xu, Xi-Xi Cao, Qi Chen, Qing-Quan Li, Wenjuan Wang, Xiao-Li Liu
Rok vydání: 2009
Předmět:
Cancer Research
Pathology
Time Factors
MMP2
Kaplan-Meier Estimate
Metastasis
Mice
Phosphatidylinositol 3-Kinases
Nude mouse
Cell Movement
Cyclin D1
Cyclin D3
Phosphorylation
rho-Associated Kinases
biology
Middle Aged
Prognosis
Neoplasm Proteins
Oncology
Matrix Metalloproteinase 2
Female
RNA Interference
Breast disease
Breast carcinoma
Adult
medicine.medical_specialty
Class I Phosphatidylinositol 3-Kinases
Mice
Nude
Breast Neoplasms
Receptors
Cell Surface
Receptors for Activated C Kinase
Transfection
GTP-Binding Proteins
In vivo
Cell Line
Tumor
Two-Hybrid System Techniques
medicine
Animals
Humans
Neoplasm Invasiveness
Protein Kinase Inhibitors
Aged
Cell Proliferation
Neoplasm Staging
Proportional Hazards Models
Carcinoma
biology.organism_classification
medicine.disease
Xenograft Model Antitumor Assays
Basigin
Cancer research
Proto-Oncogene Proteins c-akt
Zdroj: Breast Cancer Research and Treatment. 123:375-386
ISSN: 1573-7217
0167-6806
Popis: A yeast two-hybrid system was utilized to identify novel PI3K p110alpha-interacting proteins, of which receptor of activated protein kinase C1 (RACK1) was chosen for successive detailed analyses. Our aim was to investigate the function(s) of RACK1 and its involvement in mechanisms of breast carcinoma proliferation and invasion/metastasis. Experiments in breast carcinoma cell lines stably transfected with RACK1, as well as nude mouse models, showed that RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Conversely, knockdown of RACK1 by siRNA in vitro inhibited proliferation, migration, and invasion. In cell lines stably transfected with RACK1, p-AKT, cyclin D1, cyclin D3, and CD147 expression, as well as MMP2 activity, were elevated. RACK1-induced migration could be inhibited by the addition of Rho-kinase inhibitor. In 160 breast carcinoma cases, survival analyses established that RACK1 is an independent prognostic factor for poor outcome (P0.001). In conclusion, RACK1 is an independent prognosis-related factor and promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo.
Databáze: OpenAIRE
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