The Role of Dioxin Receptor in Mammary Development and Carcinogenesis
Abstract
This research is testing the hypothesis that the dioxin receptor (AhR) plays a central role in breast carcinogenesis. Following on preliminary observations of the dramatic up-regulation of AhR in advanced human breast carcinoma (HBC) cell lines, we addressed whether the overexpression of the AhR alone is sufficient to induce carcinogenic transformation in mammary epithelial cells. Overexpression of AhR in clones correlated with decrease in population doubling times subsequent to abrogation to cell cycle, enhanced motility and increased migration. Furthermore, these clones acquired the ability to invade matrigel matrix and to form colonies in soft agar. Conversely, retrovirus vectors producing siRNAs targeted against AhR were used to generate stable clones with a knockdown of 75- 90% in AhR expression. Although these clones exhibited subsequent suppression of AhR-transcriptional activity, they showed no change from the vector control clone or parent cells in population doubling times, cell cycle distribution, ability to invade matrigel matrix or to form colonies in soft agar. These results suggest that AhR alone is capable of inducing transformation of immortalized normal mammary epithelial cells into a malignant phenotype, but its depletion is insufficient to reverse the malignant phenotypes in metastatic breast cancer cells. More research is required to delineate the mechanisms of AhR involvement in breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA460788
Entities
People
- Sakina E. Eltom
Organizations
- Meharry Medical College