[Detection of cyclin A mRNA in intra-epithelial lesions of the anogenital tract induced by papillomavirus].
Human papillomaviruses (HPVs) have been recognized as likely viral agents responsible for anogenital precancer lesions and squamous cell cancers in both men and women. Nevertheless their role in carcinogenesis is not entirely clear. There are many other agents, both viral and non-viral, which might act synergistically or separately with HPV in a multistep tumorigenic process. Among non-viral factors, protooncogene and tumor suppressor gene alterations may be a major step towards the malignant transformation of an HPV-infected cell. The induction of unscheduled DNA synthesis and cell proliferation by human papillomaviruses would provide the basis for the potential of these viruses to contribute to the formation of tumors in vivo. Thus, we studied by in situ hybridization (ISH) the cyclin A gene expression in HPV-induced condylomatous and dysplastic lesions of the anogenital tract, and in inflammatory squamous intraepithelial tissues. We observed a high level of cyclin A gene expression in low grade squamous intraepithelial lesions infected by HPV type 6/11. Cyclin A induction was surprisingly more important in the upper third layers of differentiated cells together with large amounts of HPV DNA, than in proliferating basal and parabasal cells. An identical pattern was also shown in some low grade squamous intraepithelial lesions infected with potential oncogenic HPV. In contrast, there was evidence of low abundance cyclin A mRNA in most high grade squamous intraepithelial lesions induced by high risk HPV. In the inflammatory tissues, an ISH signal was sometimes detected in the basal cells. As for proliferating cell nuclear antigen (PCNA), these results observed in vivo reveal that viral oncoproteins are able to reactivate cellular DNA replication machinery to support papillomavirus DNA replication in normally differentiated, non-cycling cells. The induction of cyclin A gene expression appears to correlate with the proliferative rather than the transforming properties of these cells.
Didier
J M
JM
Laboratoire de Virologie, CHU Saint-Jacques, Besançon.
Mougin
C
C
Paterlini
P
P
Kantelip
J P
JP
Brechot
C
C
Lab
M
M
D001004:Anus Diseases / Q000235:genetics* / Q000821:virology; D016213:Cyclins / Q000235:genetics*; D005260:Female; D005831:Genital Diseases, Female / Q000235:genetics* / Q000821:virology; D005832:Genital Diseases, Male / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000302:isolation & purification; D014412:Tumor Virus Infections / Q000150:complications*
D016213:Cyclins; D012333:RNA, Messenger
Détection des ARNm de la cycline A dans les lésions intraépithéliales du tractus anogénital induites par les papillomavirus.