The Expression Of Tbx3 In Plasma Of Breast Cancer Patients And Their Clinical Significance

Tbx3 is a transcription factor of the T-box gene family. T-box gene are a group of highly conserved transcription factor homologous in the DNA binding domain, which express transcriptional control factor in eukaryote. They are characterized by having highly conserved DNA binding domain called T-domain which binds specific sequences in the promoters of the target gene. .The transcription factors coded by this family play important roles in the morphogenesis and organogenesis of vertebrates and invertebrates. All T-box transcription factors, also name as T protein, have a particular structure, all of them have the DNA binding domain comprising about 180 amino acid residues named as the T-box domain at N-terminal, in which the DNA sequence is highly conservative but the regions preceding and following the T-box domain vary in length and primary sequence. Tbx3 gene codes a peptide chain constituted by 743 amino acid residues, and DNA binding domain is located At No. 105─285 amino acids. The latest researches show that the overexpression of Tbx3 gene in mammary epithelial cells probably allows cells to have another cell divisions during its prohibiting growth or proliferative environment to continue growing. So ,the consecutive Overexpression of this gene will repeat the process mentioned above, leading to the uncontrolled growth of mammary epithelial cells and conversion of mammary epithelial cells into malignancy, which may promote the occurrence of breast cancer. The mechanisms of Tbx3 gene and its coded transcription factor Tbx3 protein in the pathogenesis of ulnar-mammary syndrome, an autosomal dominant inherited disorder. In the patients who suffer from UMS, mutation of an allele of tbx3 usually caused truncated nonfunctional protein synthesis and insufficiency of wild tbx3 protein, which is also called haploinsufficiency. Defect of functional tbx3 allele in UMS patients caused severe congenital diseases and absent of breast epithelium .Therefore ,the expression of tbx3 may play an important role in the development of breast epithelium.Tbx3 has been proved to repress the expression of the tumor suppression gene p14ARF. p14ARF is a tumor suppressor shown to be aberrantly expressed and mutated in breast cancer. In addition, p14ARF inhibits human double minute 2-mediated degradation of p53. Therefore, tbx3 repression of p14ARF decreased the half-life of p53.All these suggest that tbx3 plays a role in breast cancer development. There is experiment which proved tbx3 is overexpressed in breast cancer tissues and there is also an experiment which proved tbx3 is over expressed in the blood of breast cancer patients. but there are no experiments designed to research the expression of tbx3 both in tissue level and blood level, and the correlations of the expression of tbx3 and the clinical pathological characteristics of breast cancer patients are still not reported either.In this study, we use western blot technology to test the expression of tbx3 in plasma of the breast cancer patients. And we analyzed the correlation of the expression of tbx3 and clinical pathological characteristics. And we use fluorescence quantitative PCR to test the expression of tbx3 in breast cancer tissues and in the marginal tissues in the same patients,we also analyzed the correlation of the expression of tbx3 and clinical pathological characteristics to testify the conclusions we get from the plasma detection.The main results and conclusions of our study are as follows:1.We could detect the expression of tbx3 in the plasma of breast cancer patients.2.The expression of tbx3 gene in the plasma of breast cancer patients is significantly higher than that in the plasma of benign breast diseases patients.3.The expression of tbx3 gene in the plasma of invasive breast cancer patients in significantly higher than that in the plasma of in situ breast cancer. 4. The expression of tbx3 gene in the plasma of breast cancer patients with armpit lymph node metastasis is significantly higher that that in the plasma of breast cancer patients without armpit lymph node metastasis.5.The expression of tbx3 gene in the plasma of ER negative breast cancer patients is significantly higher that that in the plasma of ER positive breast cancer patients. 6.The expression of tbx3 gene in the plasma of Her-2 positive breast cancer patients is significantly higher than that in the plasma of Her-2 negative patients. 7.The expression of tbx3 gene in the plasma of P53 positive breast cancer patients is significantly higher than that in the plasma of P53 negative patients. 8.The expression of tbx3 in the plasma of breast cancer patients has no correlations with age and histological grade.9. The expression level of tbx3 in breast cancer tissues positively correlated with armpit lymph node metastasis ,tumor infiltrating degree, P53 status ,but has no correlations with histological grade ,age, ER and Her-2 status.