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Cyclin D1 gene expression in human cervical neoplasia
G E Nichols1, M E Williams, M J Gaffey
1Department of Pathology, University of Virginia School of Medicine, Charlottesville, USA.
Summary
Human papillomavirus (HPV) infection in cervical cancer is linked to cyclin D1 gene activity, but not necessarily increased protein levels. This suggests HPV may bypass normal cell cycle controls in cervical neoplasia.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Amplification of chromosome 11q13 leads to cyclin D1 overexpression in many carcinomas.
- Cyclin D1 and human papillomavirus (HPV) oncoproteins interact with the retinoblastoma tumor-suppressor protein.
- This suggests a common mechanism in cervical squamous cell carcinoma pathogenesis.
Purpose of the Study:
- To investigate the role of HPV and cyclin D1 in cervical neoplasia.
- To examine HPV mRNA and cyclin D1 mRNA/protein expression in cervical lesions.
Main Methods:
- RNA-mRNA in situ hybridization for HPV and cyclin D1 mRNA in 48 cervical neoplasia cases.
- Immunohistochemistry for cyclin D1 protein expression.
Main Results:
- HPV RNA detected in all 48 cases (types 6, 16, 18).
- Cyclin D1 protein was low in normal and low-grade lesions but not significantly elevated in high-grade or invasive lesions.
- Cyclin D1 mRNA overexpression was observed in various cervical lesions, including invasive squamous cell carcinoma.
Conclusions:
- Transcriptional activation of cyclin D1 occurs in HPV-associated invasive cervical carcinoma.
- This activation does not lead to increased steady-state cyclin D1 protein levels.
- Cyclin D1 protein has a limited role in HPV-associated invasive cervical squamous carcinoma pathogenesis, suggesting HPV proteins may circumvent cellular requirements for cyclin D1.