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Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis: impact of human papillomavirus infection (HPV)
Department of Biotechnology, Panjab University, Chandigarh, India / Centre for Stem Cell and Tissue Engineering, Panjab University, Chandigarh, India.ORCID iD: 0000-0003-2885-5708
Department of Biotechnology, Panjab University, Chandigarh, India.
Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Cytology and Gynae Pathology, PGIMER, Sector-12, Chandigarh, India.
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2013 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 128, no 3, 420-6 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
PML, Cervical cancer, HPV
National Category
Cancer and Oncology
Research subject
Natural sciences
Identifiers
URN: 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
Available from: 2014-04-16 Created: 2014-04-16 Last updated: 2016-10-27Bibliographically approved

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