Dissecting the role of estrogen receptor palmitoylation in breast cancer cells
Başlık çevirisi mevcut değil.
- Tez No: 402068
- Danışmanlar: DR. WEI XU
- Tez Türü: Doktora
- Konular: Göğüs Kalp ve Damar Cerrahisi, Radyasyon Onkolojisi, Radyoloji ve Nükleer Tıp, Thoracic and Cardiovascular Surgery, Radiation Oncology, Radiology and Nuclear Medicine
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2013
- Dil: İngilizce
- Üniversite: University of Wisconsin-Madison
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 169
Özet
Özet yok.
Özet (Çeviri)
Estrogen signaling is primarily mediated by two estrogen receptors (ERs), ERα and ERβ. ERα is expressed in ~70% of breast cancers and is an important diagnostic and therapeutic target. Developing better treatment options and overcoming limitations of endocrine therapy depend on a detailed understanding of ERα-signaling pathways. ERα, a member of the class I nuclear receptor superfamily of transcription factors, localizes mainly to the nucleus and interacts with DNA regulatory sequences either directly or through interaction with other transcription factors to regulate gene transcription. ERα is also rapidly activates signaling cascades. S-palmitoylation, a reversible lipid modification is catalyzed by palmitoyl acyl-transferases (PAT), which increase affinity of proteins to the membrane. Based on the results of previous studies, it is hypothesized that palmitoylation of ERα regulates extranuclear and nuclear signaling of ERα. We utilized palmitoylation-defective mutant ERαC447A-expressing MDA-MB-468 breast cancer cells to dissect the role of palmitoylation in a breast cancer cell line model. The substitution of ER palmitoylation site abrogated ERα palmitoylation,membrane localization and estrogen-dependent phosphorylation of ERK1/2 in MDAMB- 468 cell line. Besides loss of E2-dependent extranuclear signaling, the substitution of palmitoylation sites led to the loss of other ERα-dependent events in ERC447A expressing MDA-MB-468 cells, such as decreased E2-dependent S118 phosphorylation, impaired regulation of certain target genes, and loss of estrogendependent cell cycle inhibition. This study thus highlights the importance of ERα palmitoylation in both nuclear and extranuclear ER signaling pathways in breast cancer cells. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.
Benzer Tezler
- Initial characterization of CXXC5 as a putative DNA binding protein
Potensiyel olarak DNA'ya bağlanan CXXC5 proteininin ön karakterizasyonu
PELİN YAŞAR
Yüksek Lisans
İngilizce
2015
BiyolojiOrta Doğu Teknik ÜniversitesiBiyoloji Ana Bilim Dalı
DOÇ. DR. MESUT MUYAN
- Senkron saptanan aksiller lenf nodu metastazında patolojik diskordans var mı?
Is there pathological discordance in metastasis of sentinel node-detected axillary lymph nodes?
BERKAY DEMİRÖRS
Tıpta Uzmanlık
Türkçe
2024
Genel CerrahiSağlık Bilimleri ÜniversitesiGenel Cerrahi Ana Bilim Dalı
DR. MEHMET EMRAH BAYAM
- Deneysel epilepsi modelinde içeri doğrultucu potasyum kanallarının kalpteki rolü
The role of cardiac inwardly rectifying potassium channels in the experimental epilepsy model
ENES AKYÜZ
- The theoretical formation of Mise en Abyme and its intertextual applicability in Michael Cunningham's The Hours
Mise en Abyme'in teorik oluşumu ve Michael Cunningham'ın Saatler adlı eserinde metinlerarası ortaya çıkışı
EGE İBRAHİM MÜLAYİM
Yüksek Lisans
İngilizce
2023
İngiliz Dili ve EdebiyatıTekirdağ Namık Kemal Üniversitesiİngiliz Dili ve Edebiyatı Ana Bilim Dalı
PROF. DR. TATIANA GOLBAN