title: In Utero exposure to low-dose alcohol induces reprogramming of mammary development and tumor risk in MMTV-erbB-2 transgenic mice.
abstract: There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation.
authors: Julius L. Chambers Biomedical/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Kannapolis, NC 28081, USA. mzhao@nccu.edu.
authors: Zhikun
authors: Z
authors: Ma
authors: Julius L. Chambers Biomedical/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Kannapolis, NC 28081, USA. ablack18@nccu.edu.
authors: Amanda J
authors: AJ
authors: Blackwelder
authors: Julius L. Chambers Biomedical/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Kannapolis, NC 28081, USA. hlee11@nccu.edu.
authors: Harry
authors: H
authors: Lee
authors: Julius L. Chambers Biomedical/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Kannapolis, NC 28081, USA. mazhikun1225@163.com.
authors: Ming
authors: M
authors: Zhao
authors: Julius L. Chambers Biomedical/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Kannapolis, NC 28081, USA. xyang@nccu.edu.
authors: Xiaohe
authors: X
authors: Yang
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000472:pathogenicity; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D000431:Ethanol; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse