The Ah receptor (AhR) as a cytosolic protein which is well studied for its mediation of toxic responses to environmental polyhalogenated aromatic hydrocarbons (PAH) such as dioxin. Our preliminary investigation on the expression of AhR protein in human breast carcinoma (HBC) cell lines has revealed that the AhR is dramatically up-regulated in these cells, in direct proportion to their malignancy. The research we are proposing aims to establish a correlation between the AhR expression and the degree of malignancy in samples of human breast tumors of varying stages of pathogenesis (benign proliferative lesions, ductal carcinoma in situ, invasive mammary carcinoma), in comparison to normal mammary tissues. The expression of AhR mRNA and protein in these specimens will be assessed by in Situ hybridization and immunohistochemical staining, respectively. Results of immunobiochemical analyses will be correlated to the respective histopathological grade and history (clinical stage, hormone receptor and lymph node status). The proposed research aims to identify the AhR over-expression as one of the critical determinants in invasion and tumor metastasis cascade by establishing a correlation between its expression and that of these determinants. If well- established, AhR expression could be used as an independent prognostic factor, and as an early biomarker for determining the degree of cancer progression for possible early intervention.
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