Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis: impact of human papillomavirus infection (HPV)
2013 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 128, no 3, 420-6 p.Article in journal (Refereed) Published
OBJECTIVES: Cervical cancer is a leading gynecological cancer in Indian women and is caused due to infection with high risk human pappilloma virus (HR-HPV) 16 and 18. It has been well documented that PML (promyelocytic leukemia) enhances viral infectivity and plays a crucial role in antiviral response mechanisms. The aim of the present study was to evaluate the role of PML gene with context to HPV infection in cervical carcinogenesis.
METHODS: The expression pattern of PML was analyzed by western blotting and immunohistochemistry in a total of 170 fresh surgically resected cervical tissue specimens comprising precancer (n=12), cancer (n=118) and normal controls (n=40) recruited from PGIMER, Chandigarh, India. HPV status was analyzed by L1 consensus PCR followed by type specific PCR for HR-HPV types 16 and 18 and low risk types 6 and 11.
RESULTS: A significant downregulation of PML protein was observed in the majority of cervical cancer and precancer cases 68% (89/130) compared to normal controls. The loss of expression pattern of PML gene was significantly increased with severity of disease both clinically and pathologically (p<0.001). HPV infection was detected in the majority of cancer cases 96% (113/118) and in 83% (10/12) of precancer lesions whereas no infection could be detected in normal controls. Interestingly, all the 68% (89/130) cervical cancer cases that showed downregulation of PML were HPV infected (p=0.0001).
CONCLUSION: Taken together, these observations suggest that the downregulation of PML gene and its synergism with HPV infection may play an important role and may serve as a new marker for early diagnosis and therapeutic intervention for cervical carcinogenesis.
Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 128, no 3, 420-6 p.
PML, Cervical cancer, HPV
Cancer and Oncology
Research subject Natural sciences
IdentifiersURN: urn:nbn:se:his:diva-8994DOI: 10.1016/j.ygyno.2012.11.041ISI: 000315320900004PubMedID: 23220564ScopusID: 2-s2.0-84873744514OAI: oai:DiVA.org:his-8994DiVA: diva2:712801