TitleEffect of fetal alcohol on mammary carcinogenesis
NamePolanco, Tiffany (author), Cohick, Wendie S (chair), Sarkar, Dipak (internal member), Katz, Larry (internal member), Thomas, Paul (outside member), Rutgers University, Graduate School - New Brunswick,
Children of prenatal alcohol abuse,
DescriptionAltered fetal programming as a result of a suboptimal in utero environment can increase disease susceptibility in adulthood. Alcohol exposure in utero increases mammary cancer risk in rodents. Mammary development affects breast cancer risk, as a denser, hyperproliferative gland increases mammary cancer risk. Therefore we hypothesized that alcohol exposure in utero increases the action of the IGF-I/E2 system leading to hyperproliferative mammary glands and ultimately increased cancer susceptibility. We first established a model where fetal alcohol leads to increased mammary tumor susceptibility. Pregnant rats were fed a liquid diet containing ethanol (alcohol-fed), a control isocaloric liquid diet, or rat chow ad libitum. Alcohol-fed dams were acclimated to increasing concentrations of ethanol (2.2% and 4.4%), then fed 6.7% ethanol from day 7 to 21 of gestation. To investigate tumorigenesis, N-nitroso-N-methlyurea (NMU) was administered to induce tumor formation at postnatal day 50. Rats were palpated for iii tumors weekly and euthanized at 23 weeks post-NMU injection, or in a second study at 16 weeks post-injection. At 16 weeks post-injection, tumor multiplicity was greater and tumor latency was decreased in the alcohol-fed group compared to controls. At 23 weeks post-NMU injection alcohol-fed animals developed more malignant tumors and more estrogen receptor-α negative tumors with less IGF binding protein-5 expression relative to controls, indicative of poor prognosis breast cancer in women. To determine if mammary development is altered by in utero alcohol exposure, a study was conducted in which animals were euthanized prepubertally and postpubertally. Mammary glands from alcohol-fed animals showed increased proliferation and aromatase expression prior to and immediately after puberty. Mammary and hepatic IGF-I mRNA levels were also higher in alcohol-fed animals. In a separate study it was determined that alcohol-fed animals also have higher circulation E2 than controls. Together, these data indicate that alcohol exposure in utero increases susceptibility to mammary tumorigenesis, and leads to a tumor phenotype indicative of poor prognosis breast cancer. These changes may be related to enhanced early mammary development via the IGF/E2 systems. Therefore, women born to mothers who drank alcohol during pregnancy may represent a high risk group for aggressive breast cancer.
NoteIncludes bibliographical references
Noteby Tiffany Polanco
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.