Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells

نویسندگان

  • Dominika Piasecka
  • Kamila Kitowska
  • Dominika Czaplinska
  • Kamil Mieczkowski
  • Magdalena Mieszkowska
  • Lukasz Turczyk
  • Andrzej C. Skladanowski
  • Anna J. Zaczek
  • Wojciech Biernat
  • Radzislaw Kordek
  • Hanna M. Romanska
  • Rafal Sadej
چکیده

We have recently demonstrated that, fibroblast growth factor 2 (FGFR2), signalling via ribosomal S6 kinase 2 (RSK2), promotes progression of breast cancer (BCa). Loss of progesterone receptor (PR), whose activity in BCa cells can be stimulated by growth factor receptors (GFRs), is associated with poor patient outcome. Here we showed that FGF7/FGFR2 triggered phosphorylation of PR at Ser294, PR ubiquitination and subsequent receptor`s degradation via the 26S proteasome pathway in BCa cells. We further demonstrated that RSK2 mediated FGF7/FGFR2-induced PR downregulation. In addition, a strong synergistic effect of FGF7 and progesterone (Pg), reflected in the enhanced anchorage-independent growth and cell migration, was observed. Analysis of clinical material demonstrated that expression of PR inversely correlated with activated RSK (RSK-P) (p = 0.016). Patients with RSK-P(+)/PR(-) tumours had 3.629-fold higher risk of recurrence (p = 0.002), when compared with the rest of the cohort. Moreover, RSK-P(+)/PR(-) phenotype was shown as an independent prognostic factor (p = 0.006). These results indicate that the FGF7/FGFR2-RSK2 axis promotes PR turnover and activity, which may sensitize BCa cells to stromal stimuli and contribute to the progression toward steroid hormone negative BCa.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

In Silico Analysis of Sea Cucumber Bioactive Compounds as Anti-Breast Cancer Mechanism Using AutoDock Vina

In recent years, the potential of marine natural products as anticancer agents, specifically for breast cancer, has been examined. The sea cucumber (Holothuroidea: Echinodermata) is known to contain triterpene glycosides, which have shown anticancer or cytotoxic activity. In this research, molecular docking of selected sea cucumber bioactive compounds was conducted on five receptor targets that...

متن کامل

The Relationship Between Fibroblastic Growth Factor Receptor-1 (FGFR1) Gene Amplification in Triple Negative Breast Carcinomas and Clinicopathological Prognostic Factors

Background & Objective: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was t...

متن کامل

Master regulators of FGFR2 signalling and breast cancer risk

The fibroblast growth factor receptor 2 (FGFR2) locus has been consistently identified as a breast cancer risk locus in independent genome-wide association studies. However, the molecular mechanisms underlying FGFR2-mediated risk are still unknown. Using model systems we show that FGFR2-regulated genes are preferentially linked to breast cancer risk loci in expression quantitative trait loci an...

متن کامل

Effect of Extremely Low–frequency Electromagnetic Field on Apoptosis Iinduction and Expression of Estrogen Receptor, Progesterone Receptor, and ERBB2 in BT-474 Cells

Introduction: Breast cancer is the most common cancer and the first cause of cancer-related death in women worldwide. Although admirable achievements have been made in finding new therapeutic interventions, introducing efficient approaches with the least side effect is still undoubtedly demanded. Exposure to extremely-low frequency electromagnetic field (ELF-EMF) with specific parameters of fre...

متن کامل

Future of Triple Negative Breast Cancer: Can Immunotherapy Treat This Deadly Subtype of Breast Cancer?

Triple negative breast cancer (TNBC): challenges and solutions via the immune cells TNBC is one of the most complicated types of breast cancer to treat. It is generally diagnosed based on the absence of three receptors: estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) and is thus defined as a triple negative. TNBC is often more aggressive with lower survival rates...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016