ABSTRACT
Context: One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed to products containing parabens. Objective: Studies have shown that parabens impact breast cancer cell proliferation, death, migration/invasion, and metabolism, as well as gene expression in vitro. However, these studies were conducted using cell lines of European ancestry; to date, no studies have utilized breast cancer cell lines of West African ancestry to examine the effects of parabens on breast cancer progression. Like breast cancer cell lines with European ancestry, we hypothesize that parabens promote protumorigenic effects in breast cancer cell lines of West African ancestry. Methods: Luminal breast cancer cell lines with West African ancestry (HCC1500) and European ancestry (MCF-7) were treated with biologically relevant doses of methylparaben, propylparaben, and butylparaben. Results: Following treatment, estrogen receptor target gene expression and cell viability were examined. We observed altered estrogen receptor target gene expression and cell viability that was paraben and cell line specific. Conclusion: This study provides greater insight into the tumorigenic role of parabens in the progression of breast cancer in Black women.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD), and resultant non-alcoholic steatohepatitis (NASH), incidence and prevalence are rising globally due to increasing rates of obesity and diabetes. Currently, there are no approved pharmacological treatments for NAFLD, highlighting a need for additional mechanistic studies to develop prevention and/or therapeutic strategies. Diet-induced preclinical models of NAFLD can be used to examine the dynamic changes that occur during NAFLD development and progression throughout the lifespan. To date, most studies utilizing such models have focused exclusively on terminal time points and have likely missed critical early and late changes that are important for NAFLD progression (i.e, worsening). We performed a longitudinal analysis of histopathological, biochemical, transcriptomic, and microbiome changes that occurred in adult male mice fed either a control diet or a NASH-promoting diet (high in fat, fructose, and cholesterol) for up to 30 weeks. We observed progressive development of NAFLD in mice fed the NASH diet compared to the control diet. Differential expression of immune-related genes was observed at an early stage of diet-induced NAFLD development (10 weeks) and persisted into the later stages of the disease (20 and 30 weeks). Differential expression of xenobiotic metabolism related genes was observed at the late stage of diet-induced NAFLD development (30 weeks). Microbiome analysis revealed an increased abundance of Bacteroides at an early stage (10 weeks) that persisted into the later stages of the disease (20 and 30 weeks). These data provide insight into the progressive changes that occur during NAFLD/NASH development and progression in the context of a typical Western diet. Furthermore, these data are consistent with what has been reported in patients with NAFLD/NASH, supporting the preclinical use of this diet-induced model for development of strategies to prevent or treat the disease.
ABSTRACT
Intracapsular and welldefined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of premalignancy. Such alterations in histologically normal tumoradjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR1) and the lipogenic enzyme fatty acid synthase (FASN). However, the molecular etiology of prostate field cancerization, including EGR1 and FASN upregulation, remains largely unknown. It was thus hypothesized that extracellular vesicles, notably exosomes, released by tumor lesions may induce molecular alterations in the surrounding tissues, resulting in field cancerization, priming the tissue, and ultimately promoting multifocal tumorigenesis, which is often observed in prostate cancer. Towards testing this hypothesis, the current study, to the best of our knowledge, for the first time, presents correlative protein expression data, generated in diseasefree, tumoradjacent and cancerous human prostate tissues by quantitative immunofluorescence, between the exosomal marker CD9, and EGR1 and FASN. Despite the pilot character of the present study, and the static nature and heterogeneity of human tissues, the data suggest that CD9 expression itself is part of a field effect. In support of this hypothesis, the results suggest a possible contribution of exosomes to the induction of field cancerization in the prostate, particularly for EGR1. These findings were corroborated in established cell models of cancerous (LNCaP) and noncancerous (RWPE1) human prostate epithelial cells. The findings of this study warrant further investigation into the functional interface between exosomes and field cancerization, as a detailed understanding of this characterization may lead to the development of clinical applications related to diagnosis and/or prognosis and targeted intervention to prevent progression from premalignancy to cancer.
