Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most widespread cancer with increasing morbidity and mortality. FAS-associated protein with death domain (FADD) is considered as an essential instrument in cell death, whereas Bcl-XS promotes apoptosis through inhibiting the activity of Bcl-2 and Bcl-XL. OBJECTIVE AND METHODS: We detected the expression of FADD and Bcl-XS in resected NSCLC tissues by immunohistochemistry, and investigated their association with clinicopathological characteristics and prognostic significance of NSCLC patients. RESULTS: Bcl-XS expression was significantly increased in well and moderate differentiated lung SCC (P= 0.004). Lung ADC patients with overexpression of FADD and lung SCC patients with low expression of Bcl-XS had importantly lower overall survival rates by Kaplan-Meier analysis (P= 0.033, P= 0.02, respectively). Multivariate analysis confirmed that elevated expression of FADD was an independent poor prognostic factor for patients with surgically resected lung ADC (P= 0.027) and increased expression of Bcl-XS was an independent good prognostic factor for patients with surgically resected lung SCC (P= 0.016)CONCLUSION: Elevated expression of FADD was identified as independent poor prognostic factor for patients with surgically resected lung ADC, however, increased expression of Bcl-XS was an independent good prognostic biomarker for patients with surgically resected lung SCC.

Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation.

SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET-hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.

Expression of Bcl-x and Its Clinical Significance in Endometrial Cancer / 中国肿瘤临床

Objective: To investigate the roles of Bcl-xl and Bcl-xs in the development and progression of endometrial carcinoma, and to explore their correlation.Methods: The expression of Bcl-xl and Bcl-xs in 32 cases of endometrial carci-noma, 12 cases of endometrial atypical hyperplasia, 6 cases of endometrial simple hyperplasia and 10 cases of normal en-dometrial tissues were examined by RT-PCR and Western-blot.Results: The expression of Bcl-xl mRNA and protein was significantly higher in endometrial cancer tissues than in normal endometrial tissues (P<0.05), and was statistically associat-ed with the pathological stage of endometrial carcinoma.(F=5.33, P=0.02).The expression of Bcl-xs mRNA and protein in atypical endometrial hyperplasia and endometrial carcinoma tissues were significantlly lower than that in normal endometri-al tissues (P<0.05), which was also associated with clinical stage and lymph node metastasis of endometrial carcinoma (P<0.05).The expression of Bcl-xl was negatively correlated with the expression of Bcl-xs in different endometrial tissues (r=-0.76).Conclusion: The abnormal expression of Bcl-xs and Bcl-xl was a factor for the pathogenesis and development of endometrial carcinoma.The negative correlation between Bcl-xl and Bcl-xs in different endometrial tissues as well as their relative expression ratio may have certain impact on the genesis of endornetrial cancer.

The Apoptosis and Expression of Bcl-2, Bcl-xS, Bax Proteins in Fetal Brain after Treating Pregnant Mice with Endotoxin

PURPOSE: Apoptosis is active cell death which plays an important role in developing normal tissues. Various conditions such as genetic defects, drugs, ischemia or infections are known to induce apoptosis. We studied the effect of maternal infection on fetal brain development during pregnancy. METHODS: We treated 46 C3H pregnant mice with lipopolysaccharide (LPS) or phosphat-buffered saline and observed the changes in apoptosis and expression of bcl-2, bcl-xS, bax. The fetal brain tissues were removed 1-48 hours after LPS treatment. The number of apoptosis per 100 neurons and glial cells was counted in H&E stained tissue and was analyzed statistically. Immunohistochemical staining with primary antibodies of bcl-2, bcl-xS, bax was done and their expression was classified by the degree of staining. RESULTS: The number of apoptosis was increased significantly in both neurons and glial cells of LPS-treated group and its degree of staining was more remarkable in glial cells. Immunohisto chemistry for bcl-2, bcl-xS, bax oncoprotein revealed mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells, but it was more remarkable in glial cells. Immunochemistry for bcl-xS revealed no expression in neurons and minimal expression of bcl-xS in glial cells in both study groups. CONCLUSOIN: We observed an increase in the number of apoptosis, mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells of fetal brain after treating pregnant mice with LPS. Maternal infection during pregnancy may have profound effects on developing fetal brain.

The Role of Apoptosis in the Closure of Human Umbilical Vessels at Birth and Its Mechanism / 대한내과학회지

BACKGROUND: The mechanism of the closure of umbilical vessels is known to be multifactorial. In order to verify that apoptosis is one of the possible closure mechanisms, we studied to identify apoptosis in umbilical vessels and evaluate its mechanism by studying apoptosis-related gene and the relationship between the pattern of apoptosis and gestational age (GA). METHODS: Twelve umbilical cords of GA of 37-42 weeks were obtained immediatly (less than 10 min. for minimal ongoing external influences) after birth. The presence of apoptotic cells was demonstrated by electron microscopy (EM) and terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining and Western blotting were used for the analysis of the proteins of apoptosis-related gene. RESULTS: Apoptosis of the smooth muscle cells of media and intima of umbilical vessels was identified at EM, regardless of GA from 37 to 42 weeks. The proportion of TUNEL (+) cells was 80% in intima, 40% in media, 80% in connective tissue of umbilical cord. The expressions of bax-alpha, bcl-Xs/L were strong in intima, in media and connective tissue, but those of bcl-2 were detected in only in connective tissue, regardless of GA in immunohistochemistry. The ratios of expressions of bax-alpha to bcl-2, bcl-Xs to bcl-XL, did not change with increasing GA from 37 to 42 weeks in Western blotting. CONCLUSION: Apoptosis was identified in umbilical vessels. The closure of umbilical vessels can be explained by apoptosis where the ratios of bax-alpha/bcl-2, bcl-Xs/ bcl-XL play an important role. The fact that there were no differences in the extent of apoptosis and the expressions of bax-alpha/bcl-2, bcl-Xs/bcl-XL according to GA, suggests that apoptosis of umbilical vessels is more dependent on the external stimuli during delivery than GA.