Combined treatment with exogenous estradiol and progesterone increases the incidence of breast cancer in TA2 mice without ovaries.
Summary of "Combined treatment with exogenous estradiol and progesterone increases the incidence of breast cancer in TA2 mice without ovaries."
TA2 mice have a high incidence of spontaneous breast cancer without chemical stimulus. There are two proposed explanations for this phenomenon: one is gravidity and the frequency of pregnancies, and the other is related to the presence of the mouse mammary tumor virus (MMTV). MMTV is hormonally regulated and indirectly promotes tumor formation by leading to the activation of Wnt oncogenes through insertional mutagenesis. In order to clarify the relationship between estrogen, progesterone, MMTV, Wnt oncogenes and breast cancer, ovaries from virgin female TA2 mice were removed and the mice were treated with exogenous estradiol and progesterone in different patterns. This study found that the combination of exogenous estradiol and progesterone induced breast cancer formation in TA2 mice without ovaries. MMTV-LTR mRNA exhibited the highest expression in tumor tissue from the combination treatment group (CT). Mammary tissue from mice in the CT group had the highest Wnt1, Wnt5a, Wnt5b and Wnt10b mRNA expression levels. These results indicate that estradiol and progesterone act in a synergistic manner to upregulate MMTV, which subsequently induces breast cancer in TA2 mice. Various members of the Wnt gene family may play specific roles in different stages of carcinogenesis in TA2 mice.
Department of Pathology, Anhui Medical University, Hefei, Anhui Province, PR China.
This article was published in the following journal.
Name: Cancer letters
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21852035
- DOI: http://dx.doi.org/10.1016/j.canlet.2011.07.011
Medical and Biotech [MESH] Definitions
Ethinyl Estradiol-norgestrel Combination
ETHINYL ESTRADIOL and NORGESTREL given in fixed proportions. It has proved to be an effective contraceptive (CONTRACEPTIVES, ORAL, COMBINED).
A progesterone that has been used in ESTRUS SYNCHRONIZATION and has been evaluated as an injectable contraceptive in combination with estradiol enanthate. It is also used therapeutically as a topical anti-inflammatory and is applied topically in the treatment of ACNE.
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
Steroidal compounds related to ESTRADIOL, the major mammalian female sex hormone. Estradiol congeners include important estradiol precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with estrogenic activities.
Steroidal compounds related to PROGESTERONE, the major mammalian progestational hormone. Progesterone congeners include important progesterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with progestational activities.
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