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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Proepithelin is an autocrine growth factor for bladder cancer.
Francesca Lovat1, Alessandro Bitto, Shi-Qiong Xu
1Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Carcinogenesis
|February 25, 2009
Summary
Proepithelin, a growth factor, is upregulated in bladder cancer, promoting cell motility and proliferation. Its detection in urine suggests potential as a diagnostic and prognostic biomarker for bladder neoplasms.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Proepithelin is an important regulator of cell proliferation and motility.
- It is overexpressed in various cancers, including breast, ovarian, renal, and glioblastomas.
- Previous studies indicated proepithelin's role in bladder cancer cell motility.
Purpose of the Study:
- To analyze proepithelin expression in bladder cancer using bioinformatics tools.
- To investigate the functional role of proepithelin in bladder cancer cell behavior.
- To evaluate proepithelin as a potential biomarker for bladder cancer diagnosis and prognosis.
Main Methods:
- Utilized the ONCOMINE database and gene microarray analysis.
- Analyzed proepithelin messenger RNA (mRNA) expression in bladder cancer tissues versus non-neoplastic tissues.
- Employed small hairpin RNA (shRNA) to downregulate proepithelin in T24 bladder cancer cells.
- Assessed cell proliferation, migration, invasion, and wound healing.
- Detected urinary proepithelin using immunoblotting and enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Found a statistically significant increase in proepithelin mRNA expression in bladder cancers compared to normal tissues.
- Downregulation of proepithelin inhibited Akt and mitogen-activated protein kinase (MAPK) pathways, reduced proliferation, and impaired migration, invasion, and wound healing.
- Proepithelin expression was significantly upregulated in invasive bladder cancer tissues.
- Proepithelin was detectable in urine samples.
Conclusions:
- Proepithelin plays a critical role as an autocrine growth factor in bladder cancer development and progression.
- Proepithelin may serve as a novel biomarker for the diagnosis and prognosis of bladder neoplasms.
- Targeting proepithelin could be a potential therapeutic strategy for bladder cancer.
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