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

Abstract

ObjectiveGlycogen 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.MethodsImmunohistochemical 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.ResultsThe 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).ConclusionThese 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.

Different expression of GSK3β and pS9GSK3β depending on phenotype of cervical cancer: possible association of GSK3β with squamous cell carcinoma and pS9GSK3β with adenocarcinoma

“…In the present study, the expression patterns of GSK3β/pS9GSK3β and pY216GSK3β were inversely proportional in cervical cancer; higher expression of GSK3β and pS9GSK3β and lower expression of pY216GSK3β was found in both SCC and AC compared to the normal cervix, which is consistent with the previous results [913]. In cervical SCC, decreased expression of pY216GSK3β is directly associated with loss of adenomatous polyposis coli (APC) and inversely with nuclear β-catenin, suggesting that the reduction of pY216GSK3β may occur simultaneously with the disruption of GSK3β-axin destruction complex by Wnt activation [9].…”

“…A total of 84 cervical cancer specimens (64 SCC and 20 AC) with 62 CIN (31 CIN1 and 31 CIN3) and 12 normal cervical tissues were used in this study. To perform immunohistochemical staining for GSK3β, pY216GSK3β, and pS9GSK3β in the CIN, SCC, and AC tissues, we used the previously constructed tissue microarrays (TMAs) containing 62 CINs, 56 SCCs, and 7 ACs [13] as well as a newly constructed TMA containing 8 SCCs and 13 ACs. In case the tissues are lost in TMAs as they have been reused from the previous study, corresponding whole sections from the representative blocks were prepared.…”

“…In our previous work, we demonstrated that the expression of GSK3β increases with disease progression from cervical intraepithelial neoplasia (CIN) to invasive cancer, and the expression of GSK3β was higher in SCC than in AC, suggesting the possible involvement of GSK3β in the development of SCC [13]. However, only a small number of AC cases was included and there were no data on the expression of the phosphorylated forms of GSK3β (pY216GSK3β and pS9GSK3β) in that study.…”

MACC1 silencing inhibits cell proliferation and induces cell apoptosis of lung adenocarcinoma cells through the β-catenin pathway

“…Cyclin D1 is a key checkpoint of cell division from the G1 to S phase which binds its cyclin dependent kinases (CDKs) to regulate cell growth [23]. There are also extensive literature reports that Cyclin D1 plays an important role in various cancers, including NSCLC cancer [24][25][26][27].…”

Precancerous niche (PCN), a product of fibrosis with remodeling by incessant chronic inflammation

“…GSK-3b was shown to be essential in early pancreatitisinduced acinar-to-ductal metaplasia as GSK-3b ablation limited the acinar-to-ductal metaplasia [31]. Increased GSK-3b expression is associated with the lesion grade in cervical cancer and inversely correlated with Cyclin D1 [32]. Dextran sulfate sodium (DSS)induced intestinal fibrosis was improved via GSK-3b signaling and after the use of the peroxisome proliferator-activated receptor gamma (PPAR-g) modulator, GED-0507-34 Levo [33].…”