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The Expression of ALDH1、Notch4 and Numb Protein in Mammary Gland Affection and Their Correlations to Breast Stem Cell’s Improvement and Affection

Author: ZhangQingQing
Tutor: LiLianHong
School: Dalian Medical University
Course: Pathology and Pathophysiology
Keywords: mammary stem cell ALDH1 Notch4 Numb
CLC: R737.9
Type: Master's thesis
Year: 2011
Downloads: 57
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Abstract

Background and Objective: Along with deep research on the tumor origin, people realized that tumor stem cell may transform from normal stem cells or it’s precursor cells. A handful of tumor stem cells which have some capacity for self-renewal and the potencies to differentiate with multi-direction in the tumor tissue. Mammary stem cell with powerful oncocytogenetics have been abstracted in mammary tissue.The unusual expression of stem cell genes is the origination of tumor stem cell .Within the different micoenvirorment different tumor stem cells diffrentiate to different directions and form diversity tumors.Many study display that , ALDH1 is one of the potential useful stem cell markers. ALDH1 is playing the crucial role in adjusting differentiation process of stem cells. The research indicated that the cells express ALDH1 show the charactes of tumor stem cell.Notch signal pathwy plays a very important role in the development of tumor.It effects cells’proliferate、differentiation and so on. It also influence tumor stem cell.The abnormal expression of Notch gene prevent the differentiation of mammary stem cell.The mutation of Notch gene mainten mammary cellula epithelialis division growth. Notch4 is an important receptorin Notch signal pathwy.It supresses cell’s differentiation and promotes its proliferation. Numb is the inhibiting factor of Notch signal pathwy.It decides cell’s fate during restrainning Notch signal pathwy. Besides, it plays the tumor suppresion via inhibiting P53.This topic devotes to investigate the relation beween the expression of the Notch signal pathwy receptor Notch4、cell fate determinative factor Numb and the canceration of mammary stem cells factor ALDH1which have greate significants in mammary cancer reseach. Methods:10cases of normal mammary gland tissues, 25cases of mammary gland proliferated diseases,39 cases of mammary gland tumors were investigated by using S-P method of immunohistory and analyzed the expression of ALDH1、Notch4 and Numb in each tissue. And their differences in the in the types of normal、proliferated tissues ,differentiated extent and respective dependability were also studied.Results:1. ALDH1 expressions were detected in normal mammary gland tissues, proliferated and tumor tissues. Datas showed significant difference between the expressions of the three tissues (P<0.05). The expression of ALDH1 protein in mammary tumor tissue is 56.4%, it showed significant deviation existing in expressions in tumor tissues of different infiltrating types (P<0.01).2. The positve rate of Notch4 protein in normal mammary gland tissues, proliferated and tumor tissues were 10%、28%、51.3%, it showed significant deviation existing in expressions of normal as well as proliferated tissues and tumor tissues (P<0.05).3. The expression of Numb protein in normal mammary gland tissues, proliferated and tumor tissues were 60.0%、44.0%、15.4%, it showed significant deviation existing in expressions of normal as well as proliferated tissues and tumor tissues(P<0.05).4. Spearman’s rank correlation test showed that ALDH1 exprssion in breast carcinoma had positive correlation with Notch4 expression .Correlation coefficient: r=0.407,P=0.000;Notch4 exprssion in breast carcinoma had negative correlation with Numb expression.Correlation coefficient: r=-0.349,P=0.002; ALDH1 exprssion in breast carcinoma had negative correlation with Numb expression.Correlation coefficient: r=-0.341P=0.003;Conclusion:1. The significant differences between expressions of ALDH1 implied that there were“stem-like cells”exisiting in the tissue of breast tumor.The ALDH1-expressing cells in the breast carcinoma maybe the cancer stem cells of the breast carcinoma or“intermediate cells”.2. ALDH1 is probably relevant with differentiated extent.It might be an important index for evaluating the prognosis of breast tumor.3. Notch4 xpression in normal mammary gland tissues,proliferated tissues and cancerous tissues presents an increasing tendency. From the ressearch we can say that Notch signal pathway plays an important role in the formation of mammary cancer.The results from correlation analysis showed that there was strong relation between the expression of ALDH1and of Notch4,all the outcornes pointed out that Notch4 gene had some effect to the stem cell.4.Contrary to Numb, Notch4 expression low in normal mammary tissue,higer in proliferated tissues and higest in breast carcinoma. Notch4 exprssion in breast carcinoma had negative correlation with Numb expression,indicating that Numb can maitan mammary gland’s narmal development.5. The expressions of Numb and ALDH1 were detected in various mammary gland tissues, datas showed significant negtive correlation between them,which impled that during the formation of mammary stem cells, the exprssion of Numb may suppress the overexpression of ALDH1.The possible mechanism is that by degradding Notch signal pathway Numb maitains mammary stem cell develop normally.

The Expression of ALDH1、Notch4 and Numb Protein in Mammary Gland Affection and Their Correlations to Breast Stem Cell’s Improvement and Affection

Abstract

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