Role of STK15/p53 pathway and centrosome amplification in oral squamous cell carcinomas / 中国肿瘤临床

Objective: This study proposed a possible molecular mechanism underlying centrosome amplification in oral squa-mous cell carcinoma (OSCC) by analyzing the relationship of centrosome amplification with the expression of STK15 and p53 in OS-CC tissues. Methods: The expression of STK15 and p53 in formalin-fixed, paraffin-embedded tissues from 8 patients with normal oral epithelium and 43 with OSCC were quantitatively analyzed by immunohistochemistry. Centrosome status was investigated by an indi-rect-immunofluorescence double-staining method to determine the message of centrosome amplification in OSCC. The correlation of the expression of the two proteins with centrosome amplification in OSCC was statistically analyzed with SPSS13.0. Results: Normal oral epithelium showed normal centrosomes in epithelium cells, whereas 33 of the 43 OSCC cases (76.74%) showed evidence of centro-some amplification. STK15 was undetectable in normal oral epithelium. The percentage of STK15 overexpression was 67.44% in OS-CC (P=0.028). The percentage of STK15 overexpression was significantly higher in OSCC with positive p53 staining than in OSCC with negative p53 staining (P=0.01). Spearman correlation analysis indicated a correlation between STK15/p53 positive co-expression and centrosome amplification of OSCC (P=0.019). Conclusion: Centrosome amplification is a common abnormal phenomenon in OS-CC. The p53/STK15 trans-activation-independent pathway plays a role in the systemic molecular regulation of centrosome in OSCC, which leads to the occurrence of OSCC.

Prevalence of the STK15 F31I polymorphism and its relationship with mammographic density

Several studies have identified the single nucleotide polymorphism STK15 F31I as a low-penetrance risk allele for breast cancer, but its prevalence and risk association in the Brazilian population have not been determined. The goal of this study was to identify the frequency of this polymorphism in the Brazilian setting. Considering the high degree of admixture of our population, it is of fundamental importance to validate the results already reported in the literature and also to verify the relationship between this variant and breast cancer risk. A total of 750 women without breast cancer were genotyped using the TaqMan PCR assay for STK15 F31I polymorphism. Clinical information was obtained from review of the medical records and mammographic density from the images obtained using the BI-RADS System. The estimated risk of developing cancer was calculated according to the Gail model. The genotypic frequencies observed in this study were 4.5, 38.7, and 56.6 percent, respectively, for the STK15 F31I AA, AT and TT genotypes. The AT and AA genotypes were encountered significantly more often in premenopausal women with moderately dense, dense and heterogeneously dense breast tissue (P = 0.023). In addition, the presence of the TT genotype was significantly associated with age at menarche ≥12 years (P = 0.023). High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT. The genotypic frequencies observed in our Brazilian sample were similar to those described in other predominantly European populations.

Expression of STK15 in the Young Patients with Esophageal Carcinoma and Gastric Cardia Adenocarcinoma in Henan / 医学研究杂志

Objective To study the expression of STK15 in the young patients with esophageal carcinoma and gastric cardia adenocarcinoma in Henan Province, Northern China and to further understand the mechanism of esophageal and gastric cardia carcinogenesis. Methods STK15 expression was detected by immunohistochemical method (ABC) in 54 SCC and 43 GCA patients. Results The positive rate of STK15 in SCC (39% , 21/54) was lower than that in GCA (63 % , 27/43 ), and the difference was significant (P

Alternative splicing in 5'-untranslational region of STK-15 gene, encoding centrosome associated kinase, in breast cancer cell lines

Centrosomes maintain genomic stability by establishing the bipolar spindles during cell division and, execute accurate segregation of chromosomes during mitosis. In this study, we have demonstrated that there are three forms of STK-15 gene in breast cancer cell lines. Alternative splice positions are located in 5'-untranslated region of STK15 gene. The results of in vitro translation experiments revealed that the alternative splicing in the 5'-untranslated region of STK15 had no effect on protein translation. The differential expression patterns of these alternatively spliced STK15 in breast cell lines and primary tumors therefore suggest that STK15 gene transcription may be differentially regulated or stabilized in these cells.