DOI

https://doi.org/10.25772/1Q3T-7X22

Defense Date

2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Integrative Life Sciences

First Advisor

Raj R Rao, PhD

Abstract

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a high percentage of missense mutations as a result of tobacco smoking. Certain point mutations in p53 gene results in its oncogenic gain of functions (GOF), with enhanced tumorigenic characteristics beyond the loss of p53 function. However, there are no available data on characterization of lung stem cells carrying GOF mutations and correlating them with those of normal stem cells, in this study, for the first time we show that percentage of Sca-1 expressing subpopulation is significantly higher in the lungs of mice carrying p53 GOF mutations than those in lungs isolated from p53+/+ wild type mice. Further, we successfully established lung cells differentially expressing two cell surface markers, Sca-1 and PDGFR-α, with results demonstrating existence of different subpopulations of cells in the lung. Results from our project demonstrate the importance of p53 GOF mutations as correlated with specific lung cell subpopulations.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-11-2014

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