Correlation between G1 cyclins and HPV in the uterine cervix.
G1 cyclin, as a candidate proto-oncogene, plays a key role as a cellular regulator through direct interaction with retinoblastoma gene product (pRB), p107, and cyclin-dependent kinase. Human papillomavirus (HPV) 16/18 E6/7 proteins may bind the unphosphorylated pRB and act as a down-regulator of cyclin D. However, this theory has not been proven and the relationship between cyclin E and HPV also remains unclear. Using formalin-fixed and paraffin-embedded cervical tissues, we examined for HPV types 16 and 18 by nested polymerase chain reaction (PCR), and for the accumulation of cyclin D1 and E by immunohistochemistry in 22 cases of normal cervix, 23 cases of cervical intraepithelial neoplasia (CIN), 39 cases of invasive squamous cell carcinoma (SCC), and 6 cases of adenocarcinoma. Cyclin index (CI) was defined as the percentage of positively labeled nuclei per 1000 cells. The accumulation of cyclin D1 was detected in the normal basal and parabasal epithelium and was markedly decreased in neoplastic epithelium (0.87% CI in CIN, 5.88% in SCC). However, cyclin E was absent in the normal cervix but increased in neoplastic epithelium (7.17% CI in CIN, 10.32% in SCC). Cyclin D1 expression was significantly low (p = 0.004), but cyclin E expression was significantly high (p = 0.026) in HPV-positive cases. Cyclin E plays a leading role in neoplastic transformation whereas cyclin D is down-regulated, especially when associated with HPV.
Cho
N H
NH
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Kim
Y T
YT
Kim
J W
JW
D000230:Adenocarcinoma / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology; D002584:Cervix Uteri / Q000378:metabolism* / Q000821:virology*; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000821:virology
C534702:CCNG1 protein, human; D019927:Cyclin E; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019938:Cyclin D1