The Study On KAI1/CD82 Expression In Primary Breast Cancer And Its Correlation With Other Genes

With the rise in incidence of breast cancer, more and more women werefacing the threaten of breast cancer. Because the recrudescence and metastasiswere the main reason affecting the quality of survival, it was the most importancehow to control or stave the metastasis of breast cancer. The study on mechanismof tumor recrudescence and metastasis ran to gene level in molecular biology.Some tumor correlative genes had been found recently. The estimation toprognosis and individual Rx benefited from the examination of tumor correlativegenes. It would increase patients' curability greatly. We had many methods toexamine tumor genes. Such as immunohistochemistry, RT-PCR and histologicalCMOS chip technology. We detected tumor correlative genes expression in primary breast cancer byimmunohistochemistry, western blot and RT-PCR methods in this study. Theemphases were KAI1/CD82 expression in primary breast cancer and the relationto clinical or pathological factors, to patients prognosis, to other tumor correlativegenes. KAI1 is a highly conserved gene which locates on the human chromosome11p11.2-13 and codes the protein CD82 which belongs to the trarsmembrane 4superfamily (TM4SF). KAI1 could participate the reaction between cells orbetween the extracellular matrixes and the cells and had influence on themovement and the differentiate of the cells. KAT1/CD82 is an anti-metastasisgene which play an important role in the infiltration and the metastasis of tumors.It has influence on the metastasis of many kinds of tumors, such as the carcinomaof prostate, the intestinal cancer, the liver cancer, the breast cancer and so on.At present, the main methods are the chemotherapy and endocrine therapywhich can control or delay the metastasis of the breast cancer, but multidrugresistance (MDR) was the main reason that influenced on the therapeutic effect ofthe chemo. It caused the bad therapeutic effect, then appearing the recurrence andthe metastasis because the patients were insensitivity to the chemo. MDR geneMDR1 locates on the chromosome 7q21.1 which is the main factor producing thedrug resistant and codes the P-glycoprotein, shorted for P-gp, which is one of themembers of the transmembrane glycoproteins whose molecular weight is 170kD.The present researches indicated P-gp could combine with the anticancer drugs asan energy dependent drug excretion pump after the anticancer drugs entered thecells, at the same time, the nucleotide sites of which combine with ATP, and thenthe energy released after the hydrolization of ATP could make the anticancerdrugs initiatively move out of the cells to reduce the cytotoxicity. The densities ofthe drugs in the cells still remained the level couldn't kill the cells, so it couldproduce the drug resistant. But the concrete transport process and the mechanismwere still unknown. Most of the present researches indicated the positiveexpressions of MDR1/P-gp in the breast cancer patients had the relationship to thedrug resistant which was positive, and the chemo could guide the expressions ofMDR1/P-gp. The appearance of transferring the important organs from the distantwhich could affect the breast cancer patients prognosis was just because of the badchemo effect, so it showed great meaning to explore the relativity between themetastatic gene and the MDR gene.Generally thinking, the expression of the C-erbB-2 gene showed theobviously relativity to the breast cancer patients prognosis. Its higher expressioncould improve the metastatic potentiality which represented more invasion andalso could produce the drug resistant to some chemo drugs which influenced onthe therapeutic effect leading to the bad prognosis, but there was not the sameopinion about whether other genes related to the metastasis had influence on thebreast cancer patients prognosis.Nm23 is a non-metastatic gene. Most researches indicated the positiveexpression of nm23 had a negative relation to the metastasis of tumors, but theproteins coded by the normal BRCA1 genes had a depressant effect to the growthof tumors. If both of the two allelomorphic genes in BRCA1 made catastrophesbecause of the inherited and acquired reasons which led to the reducing or the lostof the functions of gene products, BRCA1 would occur the cancerization. Bcl-2had an influence on the existence of the cells as the main apoptosis repressed geneand on the promotion to the hyperplasia and the accumulating of the tumor cells.It caused the infiltration and the metastasis when the balance between theMMP-TIMP in the malignant tumors was broken up, on the other hand, promotedthe growth and the extension of the tumors by participating the palingenesis of thetumor vessels. The cell multiplication antigen tumor marker (Ki67) was animportant biological parameter, which was thought for an important tumor markerwhich had more effect in evaluating the action of the tumor cell multiplication.The expression of Ki67 related to the breast cancer clinical stage and the patient'sdisplace prognosis. P53 locates on the short arms of a chromosome. The wild typeP53 gene could cause the transformation and the cancerization to make the cellsboundless hyperplasia. The gene mutation of P53 maybe an important factorwhich is the depraved advancement of the patient's condition who are the breastcancer.We measured pathological specimen for tumor correlative genes (includingKAI1/CD82,C-erbB-2,MDR1,MMP-9,nm23,TIMP-1,BRCA1,Bcl-2,Ki67 and P53) by immunohistochemistry, western blot and RT-PCR methods inthis study. The results showed that KAI1/CD82 expressions were consistentbetween mRNA and protein. KAI1/CD82 expression had obvious correlation withmetastasis and regional lymph nodes metastasis in breast cancer (P<0.05). Thepatients with KAI1/CD82 high-expression had a good prognosis. 5-years survivalrate had an obvious rise. KAI1/CD82 expression had no correlation with clinicalor pathological types (P>0.05). Whereas it had some correlation with clinicalstages, histological grades, regional lymph nodes metastasis, beyond metastasis,ER expression (P<0.05).There was no relationship between MDR1 expression and clinical orpathological types (P>0.05). Whereas there were relativity between MDR1expression and follow factors, such as clinical stages, histological grades, regionallymph nodes metastasis, metastasis, ER and PR expression (P<0.05). C-erbB-2expression had no relationship with clinical or pathological types too (P>0.05).C-erbB-2 expression also had relativity with clinical stages, histological grades,regional lymph nodes metastasis, metastasis, ER and PR expression (P<0.05).Statistic analysis showed that CD82 had relativity with C-erbB-2, MDR1,and MMP-9 (P<0.05). CD82 had no relativity with nm23, TIMP-1, Bcl-2, Ki67,P53 (P>0.05). Metastasis of breast cancer had positive relativity with C-erbB-2,MDR1, MMP-9, P53 expression (P<0.05). Metastasis had negtive relativity withCD82,nm23,,Bcl-2,ER expression (P<0.05). Metastasis had no obviousrelativity with Ki67, PR, TIMP-1, BRCA1 expression (P>0.05).Therefore, as a tumor restraining gene, CD82 had some value for judgingprognosis of breast cancer. On the other hand, mechanism that CD82 restrainedmeastasis of tumor cells hoped for more illumination. CD82 had relativity withmany tumor correlative genes. Immunohistochemistry was a simple andconvenient method for detecting biological index of breast cancer. It may provideassistant consult or important signal for evaluating clinical or pathologicalproblems and prognosis. These would not only help clinicians to analyserecrudescence and metastasis factors, but also provide individual treatment. Atsame time, compared to single gene detection, multi-targets detection had moreadvantage.