| A proposed unified mechanism for the reduction of human breast cancer risk by the hormones of pregnancy. | |
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MedLine Citation:
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PMID: 19934340 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Parity in women is associated with reduced lifetime risk of breast cancer, and hormones of pregnancy [estrogen (E), progesterone (P), human chorionic gonadotropin (hCG)] are implicated. Parity also reduces mammary cancer risk in carcinogen-exposed rats, and administering pregnancy hormones to these animals is similarly effective. Because pregnancy hormones are also able to stimulate cancer growth, we proposed to resolve this dichotomy by determining whether administered pregnancy hormones elicit the cancer-inhibiting agent alpha-fetoprotein (AFP) from the liver, which would implicate AFP as a proximal effector of hormonal anticancer activity. Accordingly, we treated groups of nitrosomethylurea-exposed rats with saline, E(3), E(2) + P, E(3) + P, hCG, or allowed them to experience pregnancy, and then monitored mammary cancer incidence and serum levels of AFP over time. Each hormone treatment reduced mammary cancer incidence and elevated serum AFP levels. To challenge human tissues, human HepG2 liver cells in culture were treated with the same hormonal agents. Each hormone regimen increased the levels of AFP in the culture medium. Medium containing AFP elicited by hCG inhibited the E(2)-stimulated proliferation of cultured human MCF7 breast cancer cells, whereas hCG alone did not inhibit their growth. Furthermore, antibodies to AFP neutralized the growth-inhibiting effect of AFP-containing HepG2 medium. We conclude that in the treatment of carcinogen-exposed rats with the hormones of pregnancy, and by inference in women who have experienced pregnancy, that AFP is a proximal agent that inhibits mammary gland cancer. |
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Authors:
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Herbert I Jacobson; Nicole Lemanski; Anu Agarwal; Amithi Narendran; Kelvin E Turner; James A Bennett; Thomas T Andersen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-24 |
Journal Detail:
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Title: Cancer prevention research (Philadelphia, Pa.) Volume: 3 ISSN: 1940-6215 ISO Abbreviation: Cancer Prev Res (Phila) Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-05 Completed Date: 2010-04-23 Revised Date: 2010-09-16 |
Medline Journal Info:
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Nlm Unique ID: 101479409 Medline TA: Cancer Prev Res (Phila) Country: United States |
Other Details:
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Languages: eng Pagination: 212-20 Citation Subset: IM |
Affiliation:
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Center for Immunology and Microbial Diseases, Albany Medical College, NY 12208, USA. jacobsh@mail.amc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Breast Neoplasms / epidemiology, etiology* Chorionic Gonadotropin / metabolism*, pharmacology Estradiol / metabolism*, pharmacology Female Humans Mammary Neoplasms, Experimental / epidemiology, etiology Parity / physiology Pregnancy / physiology* Progesterone / metabolism*, pharmacology Rats Rats, Sprague-Dawley Risk Factors alpha-Fetoproteins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Chorionic Gonadotropin; 0/alpha-Fetoproteins; 50-28-2/Estradiol; 57-83-0/Progesterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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