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  • Title: Increased expression of SKP2 and phospho-MAPK/ERK1/2 and decreased expression of p27 during tumor progression of cervical neoplasms.
    Author: Chen TP, Chen CM, Chang HW, Wang JS, Chang WC, Hsu SI, Cho CL.
    Journal: Gynecol Oncol; 2007 Mar; 104(3):516-23. PubMed ID: 17079005.
    Abstract:
    OBJECTIVE: The objective of this study was to investigate whether the expression of SKP2, p27 and phospho-MAPK/ERK1/2 is associated with the progression of human cervical neoplasia. METHODS: We performed immunohistochemical detection to stain formalin-fixed paraffin-embedded cervical tissues with anti-SKP2 and anti-p27 monoclonal antibodies and anti-phospho-p42/44 MAPK antibody. The study sample included 23 normal cervical epithelium, 25 low-grade squamous intraepithelial lesion (LSIL), 19 high-grade squamous intraepithelial lesion (HSIL), and 31 squamous cell carcinomas (SCC). In addition, 14 frozen cervical biopsies, including 1 normal, 6 HSIL, 2 adenocarcinoma and 5 SCC, and a human cervical cancer cell line (HeLa), were analyzed the expression levels of mRNA and protein of SKP2 and p27 by RT-PCR and Western blot analysis, respectively. RESULTS: The expression of SKP2, p27 and phospho-MAPK/ERK1/2 were strongly associated with cervical neoplastic progression (P<0.0001, P=0.006, P=0.003, respectively; Fisher's Exact Test). In addition, SKP2 expression was positively correlated with phospho-MAPK/ERK1/2 expression (Spearman correlation coefficient=0.480, P=0.0002). The association between SKP2 and phospho-MAPK/ERK1/2 was significant after controlling for the four histologic grades (P=0.038, Mantel-Haenszel test). CONCLUSIONS: These results suggest that expression levels of SKP2, p27 and phospho-MAPK/ERK1/2 may serve as markers for progression in human cervical carcinoma and may also play roles in cervical carcinoma progression and cervical carcinogenesis.
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