Abstract
Purpose
To understand the pathogenesis of cervical cancer (CC) associated with polarity protein αPKC and the potential roles of αPKC in clinical management of CC.
Methods
Tissue samples were collected from women who received colposcopy biopsy or hysterectomy surgery, including 9 CIN1, 8 CIN2, 15 CIN3, and 12 invasive cervical squamous cancer (ICC). 16 normal controls were from the normal region of tumor samples, HE and immunofluorescence staining of αPKC were performed on these samples. ANOVA and Kruslal-wallis test were used to quantitate the abnormal distribution and expression level of αPKC among different cervical lesions.
Results
Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were identified in cervical lesions. In normal cervical epithelium, αPKC was detected on the apical membrane of endocervical columnar epithelial cells and of exocervical epithelial cells located at basal layer of squamous epithelium. While in squamous metaplasia, a precancerous lesion of cervical neoplasia, the polarized apical membrane localization of αPKC was disrupted, and intensed cytoplasmic accumulation was identified in the immature squamous metaplastic cells. Compared with normal cervix, number of epithelial cells with abnormal αPKC distribution was progressively increased in CINs and ICC (P < 0.05), and cytoplasmic accumulation of αPKC was increased in CIN2, CIN3, and ICC compared with CIN1 (P < 0.05).
Conclusions
Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were associated with CC progression, indicating that precise regulation of αPKC may play important roles in CC progression, and αPKC may be a potential molecular target for clinical diagnoses and treatment of CC.
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Abbreviations
- CC:
-
Cervical cancer
- ICC:
-
Invasive cervical cancer
- HPV:
-
Human papilloma virus
- CIN:
-
Cervical intraepithelial neoplasia
- αPKC:
-
Atypical protein kinase C
- H&E:
-
Hematoxylin-eosin staining
- TZ:
-
Transformation zone
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W. Huajing and Y. Pei are co-corresponding authors. This work was original research that has not been published previously. This work was supported by Ministry of education: Program for New Century Excellent Talents in University (NCET), NCET-10-0572, and by Fundamental Research Funds for the Central Universities, 2010SCU23009.
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Liu, X., Wang, L., Shen, Y. et al. Disruption of precise regulation of αPKC expression and cellular localization is associated with cervical cancer progression. Arch Gynecol Obstet 288, 401–408 (2013). https://doi.org/10.1007/s00404-013-2770-7
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DOI: https://doi.org/10.1007/s00404-013-2770-7