Abstract
Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (TZ), a narrow region of metaplastic squamous epithelium that develops at the squamocolumnar junction between the ectocervix and endocervix. It is unclear why the TZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region. We hypothesized that cells cultured from TZ are more susceptible to cellular immortalization, an alteration that contributes to malignant development. We cultured primary epithelial cells from each region of human cervix (ectocervix, endocervix and TZ) and measured susceptibility to immortalization after transfection with the complete HPV-16 genome or infection of HPV16 E6/E7 retroviruses. Cells cultured from each cervical region expressed keratin markers (keratin 14 and 18) that confirmed their region of origin. In contrast to our prediction, cells from TZ were equally susceptible to immortalization as cells from ectocervix or endocervix. Thus, increased susceptibility of the TZ to cervical carcinogenesis is not due to increased frequency of immortalization by HPV-16. We developed a series of HPV16-immortalized cell lines from ectocervix, endocervix and TZ that will enable comparisons of how these cells respond to factors that promote cervical carcinogenesis.
Highlights
Cervical cancer is a leading cause of cancer death in women worldwide [1] and persistent infection with high-risk human papillomavirus (HPV) types such as HPV16 is the major risk factor for this disease [2,3]
Cells from each region can be cultured for 2 to 4 passages before senescence, and each exhibits a distinct morphology when maintained in keratinocyte serum-free medium (KSFM) in monolayer culture (Fig 2A)
Epithelial cells cultured from human transformation zone (TZ) were not more susceptible to immortalization by HPV16 than cells from ectocervix or endocervix
Summary
Cervical cancer is a leading cause of cancer death in women worldwide [1] and persistent infection with high-risk HPV types such as HPV16 is the major risk factor for this disease [2,3]. High-risk HPV16 E6 and E7 genes are sufficient to immortalize human cervical epithelial cells [4] and cell immortalization is an important early step in malignant development [5]. Infection with high-risk HPV types is necessary for cervical cancer, it is not sufficient. HPV infections occur frequently in sexually active women, but most are recognized by the immune system and eliminated [6]. It is unclear why some high-risk HPV infections progress to cancer while many others do not
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
