BCL-2-related apoptosis markers in cutaneous human papillomavirus-associated lesions.
BACKGROUND
Human papilloma virus (HPV) is an etiological agent in benign and malignant epithelial tumors. Resistance to apoptotic stimuli by viral strategies represents an immunologic escape mechanism during virus-induced tumor development and is critical for efficient replication of the virus.


OBJECTIVE
The aim of the present study was to investigate a role of bcl-family proteins in the anti-apoptotic pathways modulated by low-risk HPVs in the development of benign HPV-associated cutaneous tumors.


METHODS
Forty lesional biopsy specimens from HPV-associated cutaneous lesions and 11 non-lesional control skin biopsies were studied by immunohistochemical analysis for the differential expressions of HPV antigens, the pro-apoptotic bax protein, and the anti-apoptotic bcl-2 and bcl-x proteins.


RESULTS
Compared with the normal epidermis, bcl-2 and bcl-x expression were significantly reduced in the lesional epidermis. Bax was expressed in HPV-associated cutaneous lesions, although the expression did not reveal a significant deviation from that in normal skin.


CONCLUSIONS
These findings indicate a discordant expression of bcl-2/ bcl-x and bax proteins in HPV-associated skin lesions and suggest that low-risk HPVs mediate other pathways that bypass the action of anti-apoptotic bcl-2 and bcl-x proteins. The presence of bax expression with a prominent decrease in bcl-2/ bax ratio and the lack of massive apoptosis in HPV-associated benign epithelial lesions may imply that interference with the pro-apoptotic proteins of bcl-family may constitute one of the several mechanisms mediated by HPV oncoproteins for the suppression of apoptotic process.
Erkek
Emel
E
Kirikkale University Faculty of Medicine, Ankara, Turkey. emelerkek@hotmail.com
Bozdoğan
Onder
O
Atasoy
Pinar
P
Birol
Ahu
A
Koçak
Mukadder
M
D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D027383:Papillomaviridae / Q000276:immunology / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D017193:Skin Diseases, Viral / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000956:Antigens, Viral; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D015415:Biomarkers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein