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Regulation of p14ARF expression by HPV-18 E6 variants.
Salvador Vazquez-Vega1, Lilia Patricia Sanchez-Suarez, Rafael Andrade-Cruz
1Department of Pathology, Hospital of Gynecology and Pediatrics 3A, Instituto Mexicano del Seguro Social, Delegación Norte, Mexico, DF, Mexico.
Journal of Medical Virology
|August 7, 2013
Summary
Human papillomavirus type 18 (HPV-18) E6 variants from different regions differentially regulate tumor suppressor proteins p53 and p14(ARF). This impacts cervical cancer development and offers insights into HPV variant oncogenesis.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Human papillomavirus type 18 (HPV-18) is a major cause of cervical cancer.
- HPV-18 has three distinct phylogenetic variants: Asian-Amerindian, European, and African.
- The E6 oncoprotein of HPV-18 regulates tumor suppressor proteins p53 and p14(ARF), which are implicated in cervical cancer.
Purpose of the Study:
- To investigate how different HPV-18 E6 variants influence the expression of p53 and p14(ARF).
- To understand the molecular mechanisms underlying the varying oncogenic potential of HPV-18 variants.
Main Methods:
- Transfection of HPV-18 E6 variants into MCF-7 cells.
- Analysis of E6 and E6* transcript levels using RT-PCR.
- Evaluation of p14(ARF) and p53 protein expression via immunocytochemistry and Western blot.
Main Results:
- Different HPV-18 E6 variants resulted in distinct ratios of E6 and E6* transcripts.
- The Asian-Amerindian variant showed E6 > E6*, while European and African variants showed E6* > E6.
- Inverse correlations were observed between E6/E6* ratios, p53 levels, and p14(ARF) expression.
Conclusions:
- Each HPV-18 E6 variant differentially regulates p53 and consequently p14(ARF) expression.
- These molecular differences may explain the varying oncogenic effects of different high-risk HPV variants in cervical cancer.
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