p120-catenin participates in the progress of gastric cancer through regulating the Rac1 and Pak1 signaling pathway.

p120-catenin (p120), an E-cadherin regulator, has been implicated as central to a series of genetic and epigenetic changes that ultimately lead to tumor progression and metastasis. Ras-related C3 botulinum toxin substrate 1 (Rac1)and p21-activated kinases (PAKs) are effectors of p120. In the present study, we examined the expression of p120, Rac1 and Pak1 using immunohistochemistry in human gastric cancer tissues. Then, we used the gastric cancer SGC7901 and AGS cell lines to explore the possible mechanism of p120, Rac1 and Pak1 in the progress of gastric cancer. Western blotting was used to detect the expression of p120, Rac1 and Pak1 in the two cell lines. Next, p120 was silenced using p120 siRNA or overexpression of p120 by transfection of the plasmid p120 1A into the two cell types, western blotting was used to investigate the expression changes of Rac1 and Pak1. Furthermore, the effects of p120 siRNA-mediated knockdown or overexpression on the proliferation and invasive ability of gastric cancer cells were investigated using wound healing test and Matrigel invasion assays. The results showed that p120 was downregulated in both poorly differentiated group and well differentiated human gastric cancer. However, Rac1 and Pak1 were upregulated in poorly differentiated tissues and remain low in well differentiated gastric cancer tissues. In the two gastric cancer cell lines, although the expression of Rac1 and Pak1 remained unchanged after the p120 knockdown, the expressions of Rac1 and Pak1 protein were decreased after p120 overexpression in both SGC7901 and AGS cells. Furthermore, knockdown of p120 promoted gastric cancer cell proliferation and invasion; overexpression of p120 reduced the proliferation and invasion of gastric cancer cells. In conclusion, based on our results, we speculate that p120 participates in the progress of gastric cancer through regulating Rac1 and Pak1, which provides a potential prevention and a promising therapeutical approach for the patients with gastric cancer.

Expressions of E-cadherin, p120ctn, ß-catenin and NF-κB in ulcerative colitis.

This study was aimed to investigate the expressions of E-cadherin, p120ctn, ß-catenin and NF-κB in ulcerative colitis (UC) tissues and the implications of their expressions in the pathogenesis of UC. The expressions of E-cadherin, p120ctn, ß-catenin and NF-κB were detected by immunohistochemistry, and those of p120ctn and NF-κB by Western blotting in 23 cases of UC and 17 cases of normal colonic tissues. The relationship between the expression of E-cadherin or NF-κB and that of p120ctn was analyzed by Spearman rank correlation analysis. The results showed that in UC and normal colonic groups, the abnormal expression rate of E-cadherin, p120ctn, ß-catenin, and NF-κB was 52.2% vs. 0 (P<0.05), 73.9% vs. 23.5% (P<0.05), 65.2% vs. 17.6% (P<0.05) and 78.4% vs. 23.5% (P<0.05), respectively. p120ctn expression was positively correlated with E-cadherin expression (r=0.404, P<0.05), but negatively with nuclear NF-κB expression (r= - 0.347, P<0.05). Western blotting showed that as compared with the normal controls, the p120ctn protein level was significantly decreased (P<0.05), whereas the NF-κB protein level was increased (P<0.05) in UC tissues. It was concluded that in the colonic tissues of UC patients, the expressions of E-cadherin, p120ctn and ß-catenin are decreased, suggesting the mucosal barrier is impaired in UC. Moreover, NF-κB is increased and activated in the UC tissues, resulting in the inflammation in UC. p120ctn may influence the UC development through modulating intercellular adhesion and inflammatory response.

Correlation of Forkhead Box c2 with subtypes and invasive ability of invasive breast cancer.

Forkhead Box c2 (FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer (BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient's age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index (LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers (71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.