Expressions of HOXA9 HOXA10 and HOXA11 in Breast Cancer
|School||Dalian Medical University|
|Keywords||Hox gene Breast cancer Estrogen and progesterone|
Objective:Breast cancer is one of the most common malignant tumor in women and its incidence rate goes upwards recent years. Estrogen and progesterone play an important role in the regulation of mammary gland development and progression of breast cancer. Therefore, it is of great significance that actively looking for downstream target genes of estrogen and progesterone effecting on breast cancer to clarify the pathogenesis and improve the therapeutic effect and prognosis of breast cancer. Recent studies have found that HOX genes expressed differently in normal breast and breast cancer, which suggested that HOX genes associated with breast cancer.HOX genes are a class of highly conserved developmental regulatory genes and plays an important regulatory role in cell proliferation, differentiation, apoptosis, and take part in development of tumors. Some scholars have reported that members of HOX gene family expressed abnormaly in breast cancer, which suggested that their expression may promote or inhibit the development of breast cancer, but the relevant researches, particularly estrogen and progesterone receptor expression in the relationship with HOX in breast cancer are rarely reported . Therefore, Purpose of this study is to detect the expression of HOXA9, HOXA10 and HOXA11, as well as relation with estrogen and progesterone receptors in breast cancer in order to further reveal the pathogenesis of breast cancer, and look for new therapeutic targets in breast cancer .Methods:The expressions of HOXA9, HOXA10 and HOXA11 were detected in 40 cases of breast cancer with ER+/ PR+ and ER-/ PR-, respectively, 11 cases with ER+/ PR- and 20 cases breast hyperplasia by immunohistochemistry; Western-blot was used to examine expressions of HOXA9, HOXA10 and HOXA11 in 30 cases of breast cancer with ER+/ PR+ and ER-/ PR-, respectively, 15 cases with ER+/ PR- and 18 cases breast hyperplasia group.Results:1. Immunohistochemical results:(1).In breast cancer, HOXA9 was expressed in the three groups, the positive signals were mainly localized in the cytoplasm,and HOXA9 expression level in ER+/ PR+ group was higher than that in ER-/ PR- group and ER+/ PR- group (P <0.05), no significant differences in expression was found between ER-/ PR- group and ER+/ PR- group(P>0.05). The expression pattern of HOXA10 was similar to HOXA9, and the positive signals were mainly localized in the cytoplasm and partly in nucleus. The expression level of HOXA10 in ER+/ PR+ group was higher than that in ER-/ PR- group and ER+/ PR- group (P <0.05), no significant differences in expression was found between ER+/ PR+ group and ER-/ PR- group(P>0.05). HOXA11-positive signal was also primarily located in the cytoplasm and partly in nucleus. There were no differences in HOXA11 expression among the three groups of breast cancer (P> 0.05).(2).In breast hyperplasia group, HOXA9 expression pattern was similar to HOXA10. The expression levels of HOXA9 and HOXA10 in the breast hyperplasia were higher than that of the breast cancer (P< 0.05). The HOXA11 protein also expressed in breast hyperplasia, but there was not difference in the expression level between breast hyperplasia and cancer.(P> 0.05).2. Western-blot results:(1).The expressions of HOXA9 and HOXA10 in breast cancer with ER+/ PR+ were higher than that with ER+/ PR-and ER-/ PR-group (P <0.05).HOXA11 protein was the highest in the ER-/ PR-group among the three groups of breast cancer (P <0.05), no significant differences in expression was found between ER+/ PR+ group and ER-/ PR- group(P>0.05).(2).HOXA9 and HOXA10 expressions in mammary hyperplasia group were lower than that of the breast cancer (P <0.05), except for no significant difference between the ER-/ PR-group and mammary hyperplasia groups (P> 0.05). There was difference in HOXA11 expression between breast hyperplasia group and cancer (P <0.05),except for the ER+/ PR- breast cancer.Conclusion:1. HOXA9 and HOXA10 protein expressions were decreased in breast cancer, which suggested that HOXA9 and HOXA10 gene played a role of anti-oncogene in the mammary tissue, and its down-regulation might be related to the occurrence of breast cancer.2. HOXA11 protein expression was increased in breast cancer, which prompted that HOXA11 play a part in oncogene in breast tissue.3. HOXA9 and HOXA10 proteins were higher in the breast cancer with ER+/ PR+ than that with ER-/ PR-group, which hinted that in the breast tissue HOXA9 and HOXA10 genes were positively regulated by estrogen and progesterone.4. HOXA11 expression was higher in the ER-/ PR-group of breast cancer than that ER+/ PR+group and ER+/ PR- group,which suggested that the progesterone had negative regulation on the HOXA11 gene in breast. HOXA11 gene over expression due to the loss of regulation by progesterone may be one of the pathogenesis of breast cancer.