Human papillomavirus-related diseases of the female lower genital tract: oncogenic aspects and molecular interaction

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• Naslov (hrvatski): Bolesti donjeg dijela ženskog spolnog sustava povezane s humanim papilomavirusom - onkogeni aspekti i molekularne interakcije
• Autor: Joško Zekan
• Autor: Mihael Skerlev
• Autor: Lukrecija Milić
• Autor: Deni Karelović
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Kliničke medicinske znanosti

Sažetak (engleski)

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of both the vulva and the vagina are also induced by HPV. Papillomaviruses are perfectly adapted to their natural host tissue, the differentiating epithelial cell of skin or mucosae, and exploit the cellular machinery for their own purposes. The infectious cycle is initiated once the infectious particles reach the basal layer of the epithelium, where they bind to and enter the cells. The critical molecules in the process of virus replication are the viral proteins E6 and E7, which interact with a number of cellular proteins. In experimental system these interactions have been shown to induce proliferation and eventually immortalization and malignant transformation of cells. Binding of E7 to pRb activates the E2F transcription factor, which then triggers the expression of proteins necessary for DNA replication. Unscheduled S-phase would normally lead to apoptosis by the action of p53. However, in HPV-infected cells, this process is counteracted by the viral E6 protein, which targets p53 for proteolytic degradation. Besides blocking p53 function in regulation of apoptosis, high-risk HPV proteins interact with both extrinsic and intrinsic apoptotic pathways. As an aberration of virus infection, constant activity of the viral proteins E6 and E7 leads to increasing genomic instability, accumulation of oncogene mutations, further loss of cell-growth control and ultimately cancer. The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus. HPV has several mechanisms for avoiding the immune system. Furthermore, HPV infections disrupt cytokine expression with the E6 and E7 oncoproteins, particularly targeting the expression of interferon genes. Approximately 10% of individuals develop a persistent infection, and it is this cohort who is at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma.

Sažetak (hrvatski)

Uzročna veza infekcije humanim papilomavirusom (HPV) i karcinoma vrata maternice potvrđena je biološki i epidemiološki. Većina karcinoma vulve i vagine također su inducirani HPV-om. Infektivni ciklus započinje kada virusne
čestice dospiju na bazalni sloj epitela gdje se vežu i ulaze u stanice. Ključne molekule u procesu virusne replikacije su
virusni proteini E6 i E7. HPV tipovi visokog rizika blokiraju funkciju p53 proteina te djeluju na ekstrinzične i intrinzične puteve apoptoze. HPV koristi brojne mehanizme za izbjegavanje humanog imunološkog sustava i mijenja ekspresiju
citokina putem E6 i E7 onkoproteina. Prosječno 10 % inficiranih osoba razvije perzistentnu infekciju i upravo je ovo
rizična skupina za razvoj prekursorskih lezija visokog rizika i invazivnog karcinoma.

• Ključne riječi (engleski): Alphapapillomavirus/isolation & purification; Female; Genital Diseases, Female/virology; Humans; Oncogenes
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Collegium Antropologicum
• Brojčani podaci: vol. 38, br. 2, str. 779-786
• p-ISSN: 0350-6134
• URN:NBN: urn:nbn:hr:105:009035
• Datum objave publikacije: 2014-06
• URL dokumenta: https://hrcak.srce.hr/127630
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 08:18:55