Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer

Mei Xu, Hui Li, Danlei Chen, Huaxun Wu, Wen Wen, Hong Xu, Jacqueline Frank, Gang Chen, Jia Luo

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Alcohol exposure increases the risk of breast cancer. Alcohol consumption by adolescents is a serious social and public health issue. This study investigated the impact of adolescent alcohol consumption on mammary tumorigenesis and progression and compared it to that of adult alcohol exposure in animal models. Methods: Female adolescent (5 weeks) and adult (8 weeks) MMTV-Wnt1 mice were exposed to alcohol either chronically or acutely. For chronic alcohol exposure, animals were fed a liquid diet containing 6.7% ethanol for 23 weeks. For acute exposure, animals were treated with ethanol (2.5 g/kg, 25% w/v) via intraperitoneal (IP) injection for 15 days. Results: In control animals, the tumor latency was 18.5 to 22 weeks. Both chronic and acute alcohol exposure in adolescent mice significantly shortened the tumor latency to 9.5 and 8.4 weeks, respectively. However, adult-initiated alcohol exposure had little effect on the tumor latency. Both adolescent- and adult-initiated alcohol exposure significantly increased lung metastasis. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased the breast cancer stem cell population. Adolescent-initiated alcohol exposure significantly altered the proliferation of mammary epithelial cells, ductal growth, and the formation of terminal end buds in the mammary glands. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased estradiol levels in the blood. Acute adolescent alcohol exposure also significantly increased blood progesterone levels. Furthermore, adolescent-initiated alcohol exposure activated PAK1 and p38γ MAPK, critical regulators of mammary tumorigenesis and aggressiveness, respectively, while adult-initiated alcohol exposure activated only p38γ MAPK. In addition, both adolescent and adult alcohol exposure significantly decreased the levels of a prognostic marker miR200b. Conclusions: Adolescent-initiated alcohol exposure enhanced both tumorigenesis and aggressiveness of mammary tumors, while adult-initiated alcohol exposure mainly promoted tumor metastasis. Thus, adolescent mice were more sensitive than adult mice in response to alcohol-induced tumor promotion.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalAlcohol: Clinical and Experimental Research
Volume47
Issue number2
DOIs
StatePublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Alcohol: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.

Keywords

  • EtOH
  • adolescents
  • cancer stem cells
  • mammary gland development
  • metastasis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Medicine (miscellaneous)
  • Toxicology
  • General Medicine

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