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The Expression And Significance Of HMOF Protein And P53Protein In Breast Cancer

Posted on:2013-05-24Degree:MasterType:Thesis
Country:ChinaCandidate:X L BianFull Text:PDF
GTID:2234330371983172Subject:Pathology and pathophysiology
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Breast cancer is one of the most common malignant tumor endanger women’shealth. It is occurred in the women who are40to60years old and premenopausal andpostmenopausal. In recent years, breast cancer incidence and mortality are of theupward trend, that is serious harm to women’s health, And has the growing concern bythe people. There are a variety of factors of incidence of breast cancer,looking fornew ways to treat or prevent breast cancer has become an important issue. In recentyears, more and more data show that epigenetic modification of tumor suppressorgenes closely related to the change, and the incidence of breast cancer.Tumor-associated genomic histone acetylation level of imbalance is a very importantfactor in breast cancer,and histone acetyltransferase play an important role in theprocess of histone acetylation。hMOF(Human Males absent on the first) as animportant member of histone deacetylase,is also called MYST1or KAT8. Recentreports indicate that hMOF mutations in the gene expression level changes play animportant role in tumorigenesis and development process, as an acetyltransferase,hMOF, mainly through regulating the expression of target genes and then in the tumoroccurs, play an important role in the development process, hMOF also has played animportant role in the silencing of tumor suppressor genes,This phenomenon has beenconfirmed。As we all know,P53is an important tumor suppressor gene, The present studywill be divided into P53wild-type (wtP53) and mutant (mtP53).The main function ofthe wild-type p53protein is involved in cell cycle regulation, in normal cells,Wild-type p53gene is easily hydrolyzed, and has short half life,but the mtp53geneproduces the protein conformation change,and increase in its stability. The mutation,remake, insert, lost, or combine to form a stable complex with other proteins of P53gene, will make it loss the function of tumor suppressor, inactivation of the P53 pathway is an important cause of cancer. Reported in the literature, hMOF has playedan important role in regulating the activity of P53pathway, reported in cervical cancer,hMOF and mtP53-protein expression was negatively correlated, But in the incidenceand development of breast cancer, the hMOF with mtP53correlation has not beenreported.In this study, using immunohistochemical staining (SP) method and molecularbiology techniques, We detected the expression of hMOF and mtP53-two proteins inbreast cancer and benign breast lesions, and analyzed the correlation with thepathological grading of breast cancer and lymph node metastasis; hMOF with breastcancer prognostic indicators of ER and PRHER-2and Ki67, mtP53of expression; andverified by PCR and Western blot analysis of our experimental results.Immunohistochemical Results1. The expression of hMOF protein is in the nucleus, hMOF expression in breastcancer is lower than the benign breast lesions; hMOF expression and pathologicalclassification of breast cancer was a negative correlation, P <0.05. The pathologyreport the hMOF positive expression rate of lymph node metastasis was lower thanthat without lymph node metastasis, P <0.05, respectively, with significant differences.hMOF protein expression and conventional clinical prognostic indicators of breastcancer patients with the ER, PR, HER-2, tumor proliferation factor Ki67proteinexpression was no significant correlation between P>0.05, but with mtP53proteinexpression was negatively correlated; In summary, hMOF expression associated withbreast cancer pathology grading, hMOF expression of the downturn is likely to play arole in the incidence of breast cancer and metastasis, can serve as a judge of breastcancer metastasis and prognosis.2. P53expression in different pathological grades of breast cancer positive rate of P53expression in volume and intensity and increased with the upgrade of the degree ofbreast cancer, P53protein expression with lymph node metastasis was significantlyassociated mtP53the abnormal gene that the patient with lymph nodetransfer of risk.3. hMOF and P53protein expression analysis in breast cancer tissue, eight cases of P53-negative breast cancer cases, the hMOF positive rate was14.5%,57cases ofP53-positive breast cancer cases, the hMOF the positive rate of45.6%, both obviousgap. Prompted both negative relationships.二.Detected by Western blot hMOF expression in breast cancer and mtP53Western blot results showed: hMOF protein expression showed a decreasing trendwith the increase in breast cancer lesions,, mtP53expression of the gradual upwardtrend, suggesting a negative correlation between the two.三.RT-PCR assay hMOF and P53expression in breast cancerThe research results of the hMOF and mtP53mRNA expression levels In breastlesions has showed that: in the50cases of breast cancer tissue, hMOF mRNAexpression levels of breast benign breast lesions showed a clear downward trend.mtP53mRNA the expression levels of benign breast showing a rising trend. WithhMOF, mtP53Immunohistochemistry and Western blot detection of consistent,suggesting that both a negative correlation.Conclusion: hMOF protein is highly expressed in invasive cancer with lowexpression in benign breast lesions. hMOF protein expression level was negativelycorrelated with the pathological classification of breast cancer. hMOF proteinexpression and lymph nodes are closely related. mtP53expression is highly expressedin breast cancer and is closely related with the degree of malignancy of breast cancerand lymph node metastasis. HMOF and mtP53protein expression was negativelycorrelated in breast cancer.
Keywords/Search Tags:hMOF protein, P53, breast cancer, histone acetylation and deacetylation
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