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作者 Rokicki, Jerzy Wayne
書名 ERBB4 regulated intramembrane proteolysis is stimulated by estradiol and the 4ICD product controls progesterone receptor expression
國際標準書號 9781124630755
book jacket
說明 124 p
附註 Source: Dissertation Abstracts International, Volume: 72-07, Section: B, page:
Adviser: Frank Jones
Thesis (Ph.D.)--Tulane University, 2011
ERBB4 is a unique member of the ERBB receptor tyrosine kinase family that can undergo regulated intramembrane proteolysis (RIP) to generate the 4ICD cytosolic fragment. ERBB4 RIP occurs upon the binding of cognate ligand. Increased levels of 4ICD have been observed after estrogen stimulation of breast cancer cells. Using cell culture, genetic, and pharmacological approaches we investigated if E2 treatment stimulates RIP. E2 stimulation lead to increased cytosolic levels of 4ICD after 60 minutes and was estrogen receptor alpha (ERalpha) dependent. Furthermore, RIP occurred thought the pathway identified for ligand induced RIP. Due to the short response time, it was hypothesized that membrane ERalpha was involved. However, it was demonstrated that non-membrane ERalpha mediates this activity
The ERBB family members ERBB1 and ERBB2 are heavily involved in the pathogenesis of breast cancer, while the role of ERBB4 is less clear. Breast cancer is the most commonly diagnosed and second leading cause of cancer related death in North American. The clinical prognosis of breast cancer is based on the expression status of a number of molecular markers, the most widely used being estrogen receptor alpha (ERalpha), progesterone receptor (PR), and ERBB2. The central role of ERalpha in the pathogenesis of breast cancer is undisputed; however, the phenotypes of ERBB4 and PR knockout mouse models overlap. Here we investigated the possibility that ERBB4 regulates estrogen stimulated PR expression in the breast. Using genetic, cell culture, and mouse model approaches we were able to demonstrate that ERBB4 coactivates PR expression in models of breast cancer and in the developing mammary gland. Furthermore, in human pathological samples, nuclear localized ERBB4/4ICD was significantly associated with increased levels of PR expression in breast tumors
School code: 0235
Host Item Dissertation Abstracts International 72-07B
主題 Biology, Molecular
Biology, Cell
0307
0379
Alt Author Tulane University. Biomedical Sciences
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