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The Sky Gene Suppresses The Malignant Growth And Metastasis Of Human Breast Cancer

Posted on:2005-06-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y B DingFull Text:PDF
GTID:1104360125951684Subject:Surgery
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Background:Spleen Tyrosine (Y) Kinase (Syk) is a protein-tyrosine kinase. Its expression has been found in various cells such as the hematopoietic, lymphocyte, fibroblast and vascular endothelial cells. Syk was extracted from porcine spleen cDNA library and therefore named as Spleen Tyrosine (Y) Kinase. Human Syk locus was mapped to be chromosome 9 at band q22, molecular weighted 72KD.Syk gene, a candidate anti-oncogene, plays a significant role in suppressing the growth and metastasis of malignant tumor. The effects of Syk on the oncogenesis and metastasis of breast carcinoma were explored. 1. Expression of Tyrosine kinase Syk in breast cancer and their clinical significance Objectives To evaluate the effects of the Syk mRNA expression in humanbreast cancer on tumor growth and metastasis, and the relation betweenexpression of the Syk gene with pathological features was also studied.Methods A panel of well-characterized human breast cancer cell lines weredetected Syk gene expression by RT-PCR(polymerase chain reaction with reversetranscription), Meanwhile, specimens from 40 breast cancer patients(tumortissues, adjacent normal tissues), 15 fibroadenoma were detected for theirexpression of the Syk gene and level of Syk mRNA.Results 3 out of 6 cell lines were not found Syk gene expression. All normalbreast tissues had the expression of the Syk gene. Unlike normal breast tissue,31 out of 40 breast cancer tissue did not show any detectable Syk mRNAexpression, there were significant difference between two groups(X2=47.4,P<0.05). The level of Syk mRNA in the primary breast cancer tissues weresignificantly lower than that in the adjacent non-cancerous breast tissues andbenign fibroadenoma breast tissues(t=3.4, P<0.05). Furthermore, only one breastcancer tissue in 18 patients with lymph node metastasis had the Syk mRNAexpression. The Syk mRNA expression was negatively correlated to lymph nodemetastasis.(X2=3.77, P<0.05).Conclusions The expression of the Syk gene may play an important role insuppressing growth and metastasis of breast cancer.2. Association of Syk protein expression with breast cancerObjective To investigate the relationship between the expression of Syk proteinand oncogenesis, metastasis in breast cancer.7Methods Using immunohistochemistry method, the expression of protein Syk,HER-2/neu, ER, PR and p53 in 40 samples with paraffin embedding weredetected.Results Of the 40 breast cancer tissue, 6 were Syk positive, 36 out of 40matched adjacent normal beast tissues were detected expression of Syk, asignificantly difference was noted between two groups(X=44.5, P<0.05). TheSyk negative cancers were associated with more lymph node metastasis(X=5.63, P<0.05). Furthermore, the Syk expression was negatively correlatedwith HER-2 and p53, no significantly difference were found between Sykexpression and ER, PR(X=2.14,P>0.05;X=0.05, P>0.05).The expression of p53was correlated with infiltration, lymph-node metastasis, clinical stage anddifferentiation degree. But there was no correlation with tumor size.Conclusion The expression of the Syk gene may play an important role insuppressing growth and metastasis of breast cancer. Syk expression is repressed ina p53-dependent.3. Hypermethylation of Syk gene in promoter region is associated withoncogenesis, metastasis of breast carcinoma.Objectives To investigate the relationship between methylation of Syk (SpleenTyrosine kinase) gene in promoter region and oncogenesis, metastasis in breastcarcinoma.Methods Using Methylation-specific PCR technique, 6 human breast cancercell lines and specimens from 40 breast cancer patients(tumor tissues, adjacent8normal tissues), were detected for their methylation of Syk promoter region.Results Methylation of Syk gene was detected in 3 out of 6 human breastcancer cell lines. No methylation of Syk promote...
Keywords/Search Tags:Syk (Spleen Tyrosine (Y) Kinase) breast carcinoma, immunohistochemistry, reverse transcriptase polymerase chain reaction, Methylation-specific PCR T lymphocyte, methylation, metastasis, ER(estrogen receptor), PR(progesterone receptor), HER-2, p53
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