Hormone receptor expression in aging mammary tissue and carcinoma from a rodent model after xenoestrogen disruption

Author(s)

Rocha Ruiz, Thalles Fernando ^[1] ; Colleta, Simone Jacovaci ^[1] ; Pires de Campos Zuccari, Debora Aparecida ^[2] ; Leite Vilamaior, Patricia Simone ^[1] ; Rivas Leonel, Ellen Cristina ^[3] ; Taboga, Sebastiao Roberto ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci, Dept Biol, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Lab Mol Invest Canc LIMC, Ave Brigadeiro Faria Lima 5416, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[3] Fed Univ Goias UFG, Inst Biol Sci ICB 3, Dept Histol Embryol & Cell Biol, Ave Esperanca S-N, Campus Samambaia, BR-74001970 Goiania, Go - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 285, NOV 15 2021.
• Web of Science Citations: 0

Abstract

Aims: Hormone receptors are the main markers applied for prognosis of breast cancer subtypes. Among modulators, exogenous chemical agents known as endocrine disruptors interact with certain receptors, triggering molecular pathways or increasing their expression. Bisphenol A (BPA), a xenoestrogen, interacts with several hormone receptors. Thus, our aim was to characterize the hormone receptor status in the mammary gland (MG) of aged female Mongolian gerbils exposed to BPA in pregnancy and lactation. Methods: We evaluated the expression of receptors for estrogens (ER alpha and ER beta), progesterone (PR), prolactin (PRL-R), HER2/ErbB2, and androgen (AR) in normal and hyperplastic mammary tissue and in carcinomas developed after BPA exposure. Key findings: BPA-exposed MG presented increased ER alpha, whereas ER beta, PR, and PRL-R showed lower expression. AR and HER2/ErbB2 showed similar expression in normal and hyperplastic tissue from control, vehicle, and BPA groups. Both receptors were found in cytoplasm and nucleus in BPA-induced carcinoma. We demonstrate the presence of EZH2 expression, an epigenetic and epithelial-mesenchymal transition (EMT) marker, with a high H score in BPA-exposed MG, which was associated with poor prognosis of cancer. Co-localization of ER alpha and EZH2 was present in normal and carcinoma features, corroborating the installation of ER alpha-positive mammary cancer associated with the EMT process. Enhanced EZH2 in BPA-exposed mammary tissue could decrease ER beta expression and promote tumorigenesis progress through HER2/ErbB2. Significance: The present study proposes the Mongolian gerbil as an experimental model for mammary carcinogenesis studies, based on BPA disruption that triggers a phenotype of increased ER alpha/HER2 positivity and depletion of ER beta/PR expression. (AU)

• FAPESP's process: 18/23383-6 - Histopathological repercussions of the endocrine disrupters bisfienol-A and 17-beta-oestradiol on mammary glands and female prostate of the Mongolian Gerbil and their relatioships with the chemically induced carcinogenesis by MNU
• Grantee: Sebastião Roberto Taboga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/01240-9 - Late effects of bisphenol A exposure in the mammary gland of female gerbils during pregnancy and lactation
• Grantee: Thalles Fernando Rocha Ruiz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/00160-1 - Effects of maternal exposure to bisphenol A on adult and senescent gerbil (Meriones unguiculatus) prostate
• Grantee: Simone Jacovaci Colleta
• Support Opportunities: Scholarships in Brazil - Doctorate