Obstet Gynecol Sci.  2016 Nov;59(6):470-478. 10.5468/ogs.2016.59.6.470.

Glycogen synthase kinase 3β and cyclin D1 expression in cervical carcinogenesis

• Park H
• Lee M
• Kim DW
• Hong SY
• Lee H

• KMID: 2378571
• DOI: http://doi.org/10.5468/ogs.2016.59.6.470

Abstract

OBJECTIVE
Glycogen synthase kinase 3β (GSK3β) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3β regulate. Our objective was to assess the expression of GSK3β and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis.
METHODS
Immunohistochemical analysis of GSK3β and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas.
RESULTS
The expression of GSK3β increased in parallel with the lesion grade, while that of cyclin D1 decreased with severity of the lesion (P<0.001). There was a significant inverse correlation between GSK3β and cyclin D1 expression in overall cervical neoplasia (Φ=-0.413, P<0.001). GSK3β expression was higher in squamous cell carcinoma than in adenocarcinoma (P=0.049).
CONCLUSION
These results suggest that the expressional increase in GSK3β plays a role in cervical carcinogenesis and has inverse correlation with cyclin D1 expression in this process. In addition, GSK3β expression appears to be associated with the histologic type of cervical cancer, especially squamous cell carcinoma.

Keyword

Cervical intraepithelial neoplasia; Cyclin D1; Glycogen synthase kinase 3 beta; Immunohistochemistry; Squamous cell carcinoma

MeSH Terms

Adenocarcinoma
Carcinogenesis*
Carcinoma, Squamous Cell
Cervical Intraepithelial Neoplasia
Cyclin D1*
Cyclins*
Glycogen Synthase Kinases*
Glycogen Synthase*
Glycogen*
Humans
Immunohistochemistry
Protein Kinases
S Phase
Uterine Cervical Neoplasms
Cyclin D1
Cyclins
Glycogen
Glycogen Synthase
Glycogen Synthase Kinases
Protein Kinases

Figure

• 

  Fig. 1 Representative immunohistochemical staining (×400) of glycogen synthase kinase 3β in cervical intraepithelial neoplasia (CIN) 1 (A), CIN3 (C), and squamous cell carcinoma (E), and of cyclin D1 in CIN1 (B), CIN3 (D), and squamous cell carcinoma (F).

• 

  Fig. 2 Squamous cell carcinoma showed moderate to strong immunoreactivity (×400) to glycogen synthase kinase 3β (A), while adenocarcinoma showed weak or negative immunoreactivity (×400) (B).

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