التفاصيل البيبلوغرافية
| العنوان: |
Investigating the role of TP63 in the squamous cell carcinoma of the skin, and head and neck cancer |
| المؤلفون: |
Lakshmana Chetty, Senthilnath |
| المساهمون: |
Koster, Maranke I., Lu, Shi-Long, Prekeris, Rytis, Fujita, Mayumi, Williams, Trevor |
| بيانات النشر: |
University of Colorado Anschutz Medical Campus. Strauss Health Sciences Library |
| سنة النشر: |
2018 |
| المجموعة: |
Digital Collections of Colorado (Colorado State University) |
| مصطلحات موضوعية: |
p63, TP63, MAPK, STAT3 Transcription Factor, Squamous Cell Carcinoma of Head and Neck, Protein Kinases |
| الوصف: |
Includes bibliographical references. ; Fall ; Cutaneous, and Head and Neck Squamous cell carcinoma (cSCC and HNSCC), are two of the most common cancers worldwide, resulting in approximately 13,700 deaths (combined) every year in the United States. Despite their high death rates, the genetic mechanisms that contribute to the development and progression of these types of SCCs are poorly understood. TP63, a master regulator of epithelial development and homeostasis, has been suggested to play a role in the development of SCCs. Herein, we investigated the role of TP63 in the initiation and progression of cSCC and HNSCC. Firstly, to determine the role of TP63 in cSCC, we performed immunostaining for TP63 and epithelial marker KRT14 on archival human cSCCs. We found that TP63 expression is either focally or completely lost in a subset of both well and poorly-differentiated cSCCs. To address the functional consequences of TP63 loss, we developed a genetically engineered mouse model and ablated all isoforms of Trp63 from the epidermis. Using this transgenic mouse, we show that Trp63 ablation followed by chemical carcinogenesis treatment (DMBA/TPA) leads to accelerated cSCC initiation and progression. To correlate these findings to humans, we generated isogenic orthotopic cSCC xenografts by downregulating TP63 expression in a human cSCC cell line (HaCaT) and implanting them into the back skin of athymic nude mice. Using this isogenic cSCC xenograft model system, we found that loss of TP63 promotes cSCC initiation and progression. Lastly, we found that loss of TRP63/TP63 expression promotes cSCC initiation and progression by activating Wnt/β-catenin signaling. Secondly, to determine the role of TP63 in HNSCC, we performed immunostaining for TP63 and epithelial marker KRT14 on archival human HNSCCs and found that TP63 expression is significantly lost in poorly-differentiated HNSCCs compared to well-differentiated HNSCCs. To address the functional consequences of TP63 loss, we used the genetically engineered mouse model as ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Lakshmanachetty_ucdenveramc_1639D_10596.pdf; https://hdl.handle.net/10968/3104Test |
| الإتاحة: |
https://hdl.handle.net/10968/3104Test |
| حقوق: |
Copyright of the original work is retained by the author. ; Embargo Expires: 06/13/2019 |
| رقم الانضمام: |
edsbas.81F4878B |
| قاعدة البيانات: |
BASE |
