ABSTRACT
Rationale: 17ß-estradiol (E2) can directly promote the growth of ERα-negative cancer cells through activation of endothelial ERα in the tumor microenvironment, thereby increasing a normalized tumor angiogenesis. ERα acts as a transcription factor through its nuclear transcriptional AF-1 and AF-2 transactivation functions, but membrane ERα plays also an important role in endothelium. The present study aims to decipher the respective roles of these two pathways in ERα-negative tumor growth. Moreover, we delineate the actions of tamoxifen, a Selective Estrogen Receptor Modulator (SERM) in ERα-negative tumors growth and angiogenesis, since we recently demonstrated that tamoxifen impacts vasculature functions through complex modulation of ERα activity. Methods: ERα-negative B16K1 cancer cells were grafted into immunocompetent mice mutated for ERα-subfunctions and tumor growths were analyzed in these different models in response to E2 and/or tamoxifen treatment. Furthermore, RNA sequencings were analyzed in endothelial cells in response to these different treatments and validated by RT-qPCR and western blot. Results: We demonstrate that both nuclear and membrane ERα actions are required for the pro-tumoral effects of E2, while tamoxifen totally abrogates the E2-induced in vivo tumor growth, through inhibition of angiogenesis but promotion of vessel normalization. RNA sequencing indicates that tamoxifen inhibits the E2-induced genes, but also initiates a specific transcriptional program that especially regulates angiogenic genes and differentially regulates glycolysis, oxidative phosphorylation and inflammatory responses in endothelial cells. Conclusion: These findings provide evidence that tamoxifen specifically inhibits angiogenesis through a reprogramming of endothelial gene expression via regulation of some transcription factors, that could open new promising strategies to manage cancer therapies affecting the tumor microenvironment of ERα-negative tumors.
Subject(s)
Neoplasms , Tamoxifen , Mice , Animals , Tamoxifen/pharmacology , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Endothelial Cells/metabolism , Angiogenesis , Gene Expression , Endothelium/metabolism , Cell Line, Tumor , Tumor Microenvironment/geneticsABSTRACT
OBJECTIVE: The aim: Was to determine the relationship between the characteristics of eating behavior with anthropometric indicators and the energy value of the diet in young people with normal weight and overweight. PATIENTS AND METHODS: Materials and methods: We examined 84 subjects of both sexes aged from 18 to 25 years. We determined their body weight, height. According to the body mass index (BMI), we formed the following groups: the control group embraced 22 men and 22 women with a BMI of 18.50-24.99 kg/m2, and the group of overweight subjects included 20 men and 20 women with a BMI of 25.00-29.99 kg/m2. We evaluated the dietary regimen using the Dutch eating behavior questionnaire (DEBQ). The obtained data were processed statistically. RESULTS: Results: Changes in eating behavior were observed in 79.55% of subjects with normal weight and 90% of overweight subjects. In people with normal body weight, the restrictive type of eating behavior prevailed, in overweight subjects, the external and emotional types were observed. CONCLUSION: Conclusions: The study established the formation of negative relationships of medium and high strength between the restrictive type of eating behavior and anthropometric indicators, as well as positive relationships of medium and high strength between indicators of emotional and external types with anthropometric indicators and energy value of diet in the subjects of both groups.