Citations

Abstract Objectives Studies on the impact of hormone replacement therapy (HRT) on hepatocellular carcinoma (HCC) have been investigated in the past. This study aims to further address this topic using a large population dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (NIH, USA). Methods Multivariable logistic regression was used for the analysis of women in the entire PLCO cohort. Results A non-significant reduction in the risk of developing HCC was observed in women using HRT compared to never users (OR=0.61, 95 % CI: 0.21–1.79, p=0.367). Oral contraceptive use was significantly associated with reduced risk of HCC in the HRT group, (OR=0.17, 95 % CI: 0.00–0.82, p=0.028), and there was a nearly-significant interaction between HRT use and oral contraceptive use (p=0.054). Regardless of HRT use, those with pre-existing liver comorbidities of hepatitis or cirrhosis were at the highest risk of developing HCC (OR=5.09, 95 % CI: 1.13–22.81, p=0.034). However, liver comorbidities of hepatitis or cirrhosis and exposure to HRT showed a significant interaction (p=0.0001). Conclusions In those taking HRT, oral contraceptive use was significantly protective against HCC, suggesting that a longer period of hormone use (oral contraceptive plus HRT) provides additional protection against HCC than HRT alone. Overall, the low numbers of HCC diagnoses, which reflect the wider healthy female population, limited our ability to establish statistical significance regarding the impact of HRT on HCC incidence, which requires further prospective studies of larger populations.

A microfluidic device was designed to efficiently fragment chromatin for downstream epigenetic assays.

Functional FOXA1 targeting is mostly unique to each of the four human cancer cell lines HepG2, LNCaP, MCF7, and T47D.

Summary The transcription factor forkhead box protein A1 (FOXA1) plays a critical role in the proliferation of human breast cancer cells, particularly estrogen receptor alpha (ERα)‐positive luminal breast cancer cells. However, genetic studies of the requirement for Foxa1 in mammary tumor formation in mice have been hampered by the lack of a conditional gene ablation. We examined three mouse models of mammary‐specific ablation of Foxa1 in ductal epithelial cells to identify the best system for complete and mammary‐specific ablation of Foxa1. We found that MMTV‐Cre and MMTV‐rtTA;Tet‐On‐Cre led to partial deletion of Foxa1 and attenuated mammary duct formation, whereas Krt14‐Cre led to complete ablation of Foxa1 and abolished mammary duct formation, in Foxa1 loxP/loxP mice. These results demonstrate that Foxa1 is essential for mammary duct formation, and reveal a series of mouse models in which mammary expression of Foxa1 can be attenuated or completely blocked. Our study also suggests a potentially powerful model for complete ablation of Foxa1 in mammary epithelial cells using Krt14‐driven Cre expression in an inducible manner, such as Krt14‐rtTA;Tet‐On‐Cre . This model system will facilitate further in vivo functional studies of Foxa1 or other factors in mammary gland development and tumor formation and progression. genesis 54:277–285, 2016. © 2016 Wiley Periodicals, Inc.

Abstract Estrogen, the female dominant hormone, has been found to play critical roles in cancers for over 100 years. In 1896, estrogen was found to promote the tumor growth of breast cancer; and in 1937, estrogen was found to prevent the tumor growth of liver cancer. After the estrogen receptor alpha (ERα) was identified in 1958, ERα-mediated estrogen signaling was found to promote or prevent the growth of breast cancer cells or liver cancer cells, respectively. Recent studies showed that ERα-mediated estrogen signaling in promoting the growth of breast cancer cells was dependent of forkhead box protein A1 (FOXA1). Our recent study showed that ERα-mediated estrogen signaling in preventing the growth of liver cancer cells also depended on FOXA factors (FOXA1 and FOXA2). Thus, FOXA-dependent ERα-mediated estrogen signaling plays opposite roles in the growth of breast cancer and liver cancer cells. Here, we applied genomic approaches to identify 184 FOXA/ER dual target genes that showed opposite expression in response to estrogen-mediated stimulation or suppression of cell growth in breast or liver cancer cells. Gene ontology analysis showed that the majority of these FOXA/ER dual target genes were involved in the processes of cell proliferation and growth, cell death, tissue development, and cancer. Manipulations of the expression of these target genes were able to reverse the growth of breast and liver cancer cells. Thus, these 184 FOXA/ER dual target genes provide us a novel set of potential biomarkers and therapeutic targets for both breast cancer and liver cancer. Note: This abstract was not presented at the conference. Citation Format: Zhaoyu Li. Comparative genomics study of FOXA/ER dual regulation in breast cancer and liver cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-08.

Abstract Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression. Nucleosome depletion during ES cell differentiation is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes. Thus, both epigenetic and genetic regulators cooperate to control nucleosome dynamics during ES cell fate decisions. Currently, we determine whether chromatin remodeling complexes are involved in nucleosome occupation. Citation Format: Zhaoyu Li. Nucleosome dynamics of cell differentiation. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A34.