AbstractBASP1 is a multifunctional protein which has been found to regulate transcription in several different cell lines through acting as a co-factor for WT1 or ERα. BASP1 has been reported to possess either tumour suppressor or tumour promoting activity in multiple cancer types across multiple tissues. In breast cancer cells, BASP1 acts as a tumour suppressor and enhances the effects of tamoxifen treatment. Tamoxifen is an ER modulator commonly used to treat breast cancer but long term treatment is strongly associated with increased risk of endometrial cancer occurrence. Although tamoxifen acts as an ER antagonist in the breast, in the endometrium, tamoxifen acts as an ER agonist.
This study investigated the expression and functions of BASP1 in Ishikawa endometrial cancer cells, as well as its effects on tamoxifen action. After confirming the presence of endogenous BASP1 in Ishikawa cells, cell line derivatives were generated that either knock down or overexpress BASP1. These cells were used to determine how BASP1 regulates cell growth, tumourigenicity and transcription of ER target genes. BASP1 was found to be primarily cytoplasmic in Ishikawa cells but still affected the transcription of a subset of ERα target genes. BASP1 was also found to reduce proliferation and colony formation efficiency in Ishikawa cells, indicating tumour suppressor activity. qPCR analysis revealed that BASP1 enhances the effects of tamoxifen treatment on the expression of a subset of ERα target genes: PGR, Greb1 and TFF1.
The tumour suppressor activity of BASP1 in Ishikawa cells and the modulation of tamoxifen action is similar to that which was reported in breast cancer cells. However, in Ishikawa cells, BASP1 targeted a different set of ER target genes. The work presented here suggests that BASP1 may play a role in the differential effects of Tamoxifen in different cell types.
|Date of Award||6 Nov 2018|
|Supervisor||Stefan G E Roberts (Supervisor)|