ABSTRACT
Objective:To explore the cooperation and clinical significance of HIF-1α,ALDH1 and Hedgehog signaling pathway in the activation of cancer stem cell(CSC) in triple negative breast cancer(TNBC).Methods: ALDH1+(Aldehyde dehydrogenase1)breast cancer stem cells and ALDH1-breast cancer cells were selected from MDA-MB-231 cells by magnetic activated cell sorting system(MACS),qRT-PCR method was employed to analyze the expression differences of HIF-1α and Hedgehog signaling molecules Sonic hedgehog(SHH),patched1(PTCH1),Smoothened(SMO) and Glioma-associated oncogene homoglog1(GLI1) in ALDH1+ breast cancer stem cells and ALDH1-breast cancer cells.Immunohistochemical method was applied to study the expressions of HIF-1α and ALDH1 and the relationships among HIF-1α,ALDH1 and Hedgehog signaling molecules in TNBC.Results: The expressions of HIF-1α mRNA,SMO mRNA and GLI1 mRNA in ALDH1+ breast cancer stem cell were higher than those in ALDH1-breast cancer cell(P all<0.05).The positive expression rates of HIF-1α were 90.0% and 70.0%,and the positive rates of ALDH1 were 93.3 % and 66.7 % in TNBC and non-TNBC,respectively(P all<0.05).Spearman rank correlation analysis showed that the expression of HIF-1α was positively related with that of ALDH1 in TNBC(r=0.53,P<0.01).HIF-1α expression was correlated with lymph node metastasis and TNM stage(P all<0.05),ALDH1 expression was correlated with histological grade and TNM stage(P all<0.05).In addition,the expression of HIF-1α was positively related with that of Hedgehog signaling molecules SHH(r=0.584,P<0.01),SMO(r=0.467,P<0.01) and GLI1(r=0.439,P<0.05),the expression of ALDH1 was positively related with that of SHH(r=0.426,P<0.05) and GLI1(r=0.394,P<0.05).Conclusion: HIF-1α and Hedgehog signaling pathway were activated in ALDH1+ breast cancer stem cell.HIF-1α,ALDH1 and Hedgehog molecules may cooperate with each other to activate breast CSC to promote the malignant progression of TNBC.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mitochondrial DNA (mtDNA) five coding region sequence polymorphisms encompassing positions nt3954-4506, nt5218-5974, nt7942-8711, nt10296-10653, and nt14496-14867 in Chinese Han population of Yanbian area, Jilin province.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) and direct sequencing method were used to detect the haplotype distribution of mtDNA coding region in 200 unrelated Chinese Han individuals.</p><p><b>RESULTS</b>One hundred and ten haplotypes were observed in the 200 individuals. The gene diversity was 0.9879 and the random match probability was 0.0171. Compared with the Anderson's sequence,81 nucleotide variants were obtained,of which 66 were previously registered in MITOMAP,and 15 were novel.</p><p><b>CONCLUSION</b>The obtained data suggest that these sequence polymorphisms are valuable genetic markers for personal identification when added to mtDAN control region investigation, and thus could be used as basic data for the forensic application in Chinese Han population.</p>