title: Inhibition of Mammary Cancer Progression in Fetal Alcohol Exposed Rats by β-Endorphin Neurons.
abstract: BACKGROUND
  Fetal alcohol exposure (FAE) increases the susceptibility to carcinogen-induced mammary cancer progression in rodent models. FAE also decreases β-endorphin (β-EP) level and causes hyperstress response, which leads to inhibition of immune function against cancer. Previous studies have shown that injection of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) into the third ventricle increases the number of β-EP neurons in the hypothalamus. In this study, we assessed the therapeutic potential of stress regulation using methods to increase hypothalamic levels of β-EP, a neuropeptide that inhibits stress axis activity, in treatment of carcinogen-induced mammary cancer in fetal alcohol exposed rats.
  
  
  METHODS
  Fetal alcohol exposed and control Sprague Dawley rats were given a dose of N-Nitroso-N-methylurea (MNU) at postnatal day 50 to induce mammary cancer growth. Upon detection of mammary tumors, the animals were either transplanted with β-EP neurons or injected with dbcAMP-delivering nanospheres into the hypothalamus to increase β-EP peptide production. Spleen cytokines were detected using reverse transcription polymerase chain reaction assays. Metastasis study was done by injecting mammary cancer cells MADB106 into jugular vein of β-EP-activated or control fetal alcohol exposed animals.
  
  
  RESULTS
  Both transplantation of β-EP neurons and injection of dbcAMP-delivering nanospheres inhibited MNU-induced mammary cancer growth in control rats, and reversed the effect of FAE on the susceptibility to mammary cancer. Similar to the previously reported immune-enhancing and stress-suppressive effects of β-EP transplantation, injection of dbcAMP-delivering nanospheres increased the levels of interferon-γ and granzyme B and decreased the levels of epinephrine and norepinephrine in fetal alcohol exposed rats. Mammary cancer cell metastasis study also showed that FAE increased incidence of lung tumor retention, while β-EP transplantation inhibited lung tumor growth in both normal and fetal alcohol exposed rats.
  
  
  CONCLUSIONS
  Our results suggest that increase of β-EP production in the hypothalamus may serve as a potential therapeutic strategy for treating the cancer growth in patients with chronic stress and compromised immune function, such as the patients with FAE.
authors.affiliation: Endocrine Program, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.|Endocrinolgy and Animal Biosciences Graduate Program, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Endocrine Program, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.|Molecular Biosciences Graduate Program, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.
authors.forename: Tina
authors.initials: T
authors.lastname: Franklin
authors.affiliation: Endocrine Program, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.|Department of Animal Sciences, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D004198:Disease Susceptibility; D004837:Epinephrine / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D053804:Granzymes / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008770:Methylnitrosourea / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D000477:Alkylating Agents; D002492:Central Nervous System Depressants; D016207:Cytokines; D000431:Ethanol; D001615:beta-Endorphin; D003994:Bucladesine; D008770:Methylnitrosourea; D007371:Interferon-gamma; D053804:Granzymes; D009638:Norepinephrine; D004837:Epinephrine
keywords: Beta-Endorphin; Breast Cancer; Cancer Prevention; Fetal Alcohol; Stress Control