Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix.
Cell Proliferation
Cell Transformation, Neoplastic
/ metabolism
Cervix Uteri
/ metabolism
CpG Islands
Epithelial Cells
/ metabolism
Female
Humans
In Situ Hybridization
In Situ Hybridization, Fluorescence
Metaplasia
/ etiology
Methylation
Papillomaviridae
/ genetics
Papillomavirus Infections
/ metabolism
Promoter Regions, Genetic
SOXB1 Transcription Factors
/ metabolism
SOXF Transcription Factors
/ metabolism
Squamous Intraepithelial Lesions of the Cervix
/ etiology
Stem Cells
/ metabolism
SOX17
SOX2
cervical preneoplasia
keratins
reserve cells
squamocolumnar junction
squamous intraepithelial lesions
transformation zone
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
24
03
2020
revised:
28
04
2020
accepted:
11
05
2020
pubmed:
10
7
2020
medline:
8
6
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
The dynamics and topographical distribution of SOX17 and SOX2 expression was studied in the transformation zone (TZ) of the uterine cervix. This TZ is a dynamic area where switches from glandular into squamous epithelium can be recognized, new squamocolumnar junctions are formed, and premalignant lesions originate. SOX17 and SOX2 show mutually exclusive expression patterns in the normal uterine cervix, with SOX2 being exclusively found in squamous epithelium, while SOX17 is detected in endocervical columnar cells and reserve cells. Normal cervices and squamous intraepithelial lesions (SIL) were studied with immunohistochemistry, methylation of SOX17, human papilloma virus (HPV) genotyping, and in situ hybridization. In the TZ squamous metaplasia originating from these reserve cells can still show SOX17 expression, while also remnants of SOX17-positive immature metaplasia can be recognized in the normal squamous epithelium. SOX17 expression is gradually lost during maturation, resulting in the exclusive expression of SOX2 in the majority of (SIL). This loss of SOX17 expression is independent of methylation of the CpG island in its promotor region. HPV can be detected in SOX17-positive immature metaplastic regions in the immediate vicinity of SOX2-positive SIL, suggesting that switches in SOX17 and 2 expression can occur upon HPV infection. This switch in expression, and the strong association between the distribution of reserve cells and squamous areas within the columnar epithelium in the TZ, suggests that reserve cell proliferations, next to basal cells in the squamous epithelium, are potential targets for the formation of squamous lesions upon viral infection.
Identifiants
pubmed: 32644288
doi: 10.1002/cam4.3201
pmc: PMC7476841
doi:
Substances chimiques
SOX17 protein, human
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
SOXF Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6330-6343Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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