Poster abstracts

Poster number 22 submitted by Yanping Shen

Regulation of M-phase cell-cycle gene UBE2C in breast cancer by estrogen receptor

Yanping Shen (OSBP), Qianben Wang (Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center)

Abstract:
The UBE2C protein is an anaphase promoting complex/cyclosome (APC/C)-specific E2 ubiquitin-conjugating enzyme involved in APC/C- dependent M-phase cell progression. Considering its important role in M-phase cell cycle regulation, it is not surprising that UBE2C functions as a prominent oncogene in many solid tumors including late-stage prostate cancer and breast cancer. While our recent studies found that androgen receptor (AR) drives UBE2C overexpression in late-stage prostate cancer, little is known about the underlying regulatory mechanisms of the overexpression of UBE2C, an estrogen-regulated gene, in breast cancer.
Estrogen receptor (ER) is the defining feature of luminal breast cancers, where it functions as a transcription factor to regulate cell division. Previous mapping of the ER cistrome in the breast cancer cell line MCF-7 has identified an ER binding site located -32.8 kb away from the transcription start site (TSS) of UBE2C gene. However, it is unknown whether UBE2C is an ER direct target gene in breast cancer cells. In the current study, we confirmed that ER bound at the putative UBE2C enhancer region in MCF-7 cells by using direct chromatin immunoprecipitation (ChIP). We also found that the pioneer transcription factor for ER, FoxA1, was also recruited to the putative UBE2C enhancer region. Real time RT-PCR analysis showed that UBE2C expression level was decreased after ER or FoxA1 silencing, and increased after estrodiol (E2) treatment of MCF-7 cells. These data indicate that UBE2C is an ER and FoxA1 co-regulated direct target gene in MCF-7 cells. We are currently characterizing the UBE2C enhancer in more detail, and examining the functional significance of UBE2C in MCF-7 and other ER positive breast cancer cells.

References:
1. Wang Q, Carroll JS and Brown M. Spatial and Temporal Recruitment of Androgen Receptor and Its Coactivators Involves Chromosomal Looping and Polymerase Tracking. Molecular Cell 2005; 19: 631–642.
2. Carroll JS, Meyer CA, Song J et al. Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006; 38:1289-1297.
3. Lupien M, Eeckhoute J, Meyer CA et al. FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription. Cell. 2008; 132:958-970.

Keywords: UBE2C, FoxA1, estrogen receptor