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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


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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).
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Figure 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).

Mentions: The staining pattern of GSK3β and cyclin D1 in precancerous and cancerous cervix tissues is shown in Fig. 1. GSK3β was negative in normal epithelia, but cyclin D1 immunostaining was positive in the basal and parabasal epithelia of all normal cervical specimens. p16 was stained with patchy or diffuse basal pattern in all CIN1 specimens. All CIN3 and SCC specimens showed moderate to strong p16 staining with diffuse basal pattern. The expression of GSK3β increased with progression of disease from CIN1 (3.2%) to CIN3 (54.8%) to cancer (76.2%). Most specimens of CIN1 showed no immunoreactivity of GSK3β. In CIN3, immunostaining for GSK3β was mostly weak and strong immunostaining was observed in cancer tissues only. Cyclin D1, found present in all normal (12/12) and CIN1 specimens (31/31), decreased with disease progression but slight increase was observed in cancer (12.7%) compared to CIN3 (9.7%) (Table 1).


Glycogen synthase kinase 3 β and cyclin D1 expression in cervical carcinogenesis
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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120066&req=5

Figure 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).
Mentions: The staining pattern of GSK3β and cyclin D1 in precancerous and cancerous cervix tissues is shown in Fig. 1. GSK3β was negative in normal epithelia, but cyclin D1 immunostaining was positive in the basal and parabasal epithelia of all normal cervical specimens. p16 was stained with patchy or diffuse basal pattern in all CIN1 specimens. All CIN3 and SCC specimens showed moderate to strong p16 staining with diffuse basal pattern. The expression of GSK3β increased with progression of disease from CIN1 (3.2%) to CIN3 (54.8%) to cancer (76.2%). Most specimens of CIN1 showed no immunoreactivity of GSK3β. In CIN3, immunostaining for GSK3β was mostly weak and strong immunostaining was observed in cancer tissues only. Cyclin D1, found present in all normal (12/12) and CIN1 specimens (31/31), decreased with disease progression but slight increase was observed in cancer (12.7%) compared to CIN3 (9.7%) (Table 1).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus