Khadijeh Jamialahmadi
Mashhad University of Medical Sciences, Iran
Title: Gankyrin: A novel gene that promotes tamoxifen resistance in breast cancer patients
Biography
Biography: Khadijeh Jamialahmadi
Abstract
Breast cancer is the most frequent malignancy in women worldwide. Oestrogen receptor α (ERα) antagonists like tamoxifen are used in endocrine therapies for ERα-positive (ERα+) breast cancer patients. Unfortunately, the clinical benefit is limited due to intrinsic and acquired drug resistance. Gankyrin (P28GANK) is a newly defined oncoprotein which was reported to confer a multidrug resistant phenotype in some cancer cells. Gankyrin also functions as a dual-negative regulator of the two most important tumor suppressor pathways: (I) INK4-CDK-pRb, and (II) ARF-MDM2-p53. In the present study, the levels of protein expression and mRNA transcripts were determined using immunohistochemical analysis and Real-Time quantitative PCR in 72 matched formalin-fixed paraffin-embedded and fresh frozen breast cancer tissues (36 tamoxifen resistant and 36 tamoxifen sensitive). Overexpression of P28GANK was present in about 56% of the tamoxifen sensitive breast cancer patients and more frequently (91%) in tamoxifen-refractory tumors. P28GANK gene was also found to be overexpressed at the protein level in tamoxifen resistance patients compared to tamoxifen sensitive samples (p=0.045). These results for the first time suggest that Gankyrin plays a role in tamoxifen-resistant breast cancer, and the inhibition of this oncoprotein may be a potential target for re-sensitizing the resistant breast cancer patients to tamoxifen-treatment in endocrine-resistant breast cancer patients.