The Expression And Significance Of BRCA1 And IGF1R In Breast Malignant And Benign Tumors

Background and ObjectiveBreast cancer is one of the most common malignancies among women.Until now, its etiology has not been fully understood.Now,cumulative experimental results suggest that breast cancer susceptibility gene one(BRCA1) and the insulin-like growth factor-Ⅰreceptor(IGF-IR) play an important role in breast cancer development and progression.BRCA1 is a tumor suppressor gene,which normally function as a negative regulator of the cell cycle,DNA damage repair and may be an active inhibitor of neoplastic generation.Germline alteration of BRCA1 is well known to cause familial breast cancer.Mutation of the BRCA1 gene has been demonstrated in 80%of familial breast cancer.Somatic mutation of the BRCA1 gene are rare in sporadic breast cancers,but a high incidence of reduced or lost the expression of BRCA1 protein in sporadic breast cancers has been demonstrated.These evidences suggest that BRCA1 gene might have an important affect in sporadic breast cancers.The insulin-like growth factor-Ⅰreceptor is a tyrosine kinase,transmembrane receptor expressed in most body tissues and required for normal growth of cells.By binding to the IGFs,IGF-IR can mediate the biological actions of the IGFs,which can promote cell proliferation and inhibit apoptosis. A number of documents reported that the insulin-like growth factor type one receptor was overexpressed in most breast cancers,and had a critical role in breast cancer etiology.As a growth regulatory factor,expression of the IGF-IR gene is under inhibitory control by a number of transcription factors with tumor suppressor activity,such as BRCA1 and p53,and so on.Recently,some experimental results displayed that the IGF-IR gene was a novel downstream target for BRCA1 action.BRCA1 was able to suppress IGF-IR promoter activity,and regulate the expression of IGF-IR protein in tumor cells.So far,the relationship between IGF-IR and BRCA1 in breast cancer is unclear.Our study is designed to investigate the expressions of IGF-IR and BRCA1 in breast cancer and breast fibroadenoma tissues,and study the correlation of the expressions of IGF-IR,BRCA1 with pathological parameters,including tumor size,tumor type,histological grade and axillary nodal status,so as to evaluate the significance of IGF-IR and BRCA1 as the diagnosis,treatment and the prognostic indexes.MethodsThe expressions of BRCA1 and IGF-IR of breast cancer tissues taken from 42 breast cancer patients as well as 30 breast fibroadenoma patients were examined using immunohistochemical SABC method.We analyzed the correlation of the results with other parameters which included tumor size,tumor type,histological grade and axillary nodal status.Results1) The expression of IGF-IR was 88.1%in breast cancer patients and 46.7 %in breast fibroadenoma patients.No significant correlation was observed between expression of IGF-IR and tumor size,tumor type,histological grade and axillary nodal status(all P＞0.05).2) The expression of BRCA1 was 52.4%in breast cancer patients and 86.7% in breast fibroadenoma patients.The lower rate of the expression of BRCA1 was found in axillary lymph nodes metastases(P＜0.05).The positive expression rate in stageⅢof breast cancer was lower than that in stageⅠ(P＜0.05)and was also lower than that in stageⅡ(P＜0.05),but there was no significant difference between stageⅠand stageⅡ(P＞0.05).No significant correlation was observed between expression of BRCA1 and tumor size,tumor type(all P＞0.05).3)There was no significant correlation between the positive expression rate of BRCA1 and the level of IGF-IR expression in breast cancer patients(x~2=1.620 P＞0.05).ConclusionsThe level of BRCA1 expression of breast cancer was lower than that breast fibroadenoma.The level of IGF-IR expression of breast cancer was higher than that breast fibroadenoma.These dates suggested that BRCA1,IGF-IR play an important role in pathogenesis and development of breast cancer.They may be a adjuvant index for diagnosing,estimating prognosis and targeting gene therapy to breast cancer. In addition,BRCA1 and IGF1R are independent of each other in breast cancer pathogenesis and development.