Exposure to Excess Estradiol or Leptin during Pregnancy Increases Mammary Cancer Risk and Prevents Parity-Induced Protective Genomic Changes in Rats
| Autor: | Kerrie B. Bouker, Mingyue Wang, Sonia de Assis, Lu Jin, Leena Hilakivi-Clarke |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Leptin
Cancer Research medicine.medical_specialty 9 10-Dimethyl-1 2-benzanthracene DMBA Apoptosis Biology Real-Time Polymerase Chain Reaction Article Immunoenzyme Techniques Rats Sprague-Dawley Mammary Glands Animal Breast cancer Pregnancy Risk Factors Internal medicine Biomarkers Tumor medicine Animals RNA Messenger reproductive and urinary physiology Carcinogen Cell Proliferation Oligonucleotide Array Sequence Analysis Estradiol Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Mammary Neoplasms Experimental Estrogens Genomics medicine.disease Rats Parity Cell Transformation Neoplastic Endocrinology Real-time polymerase chain reaction Oncology Carcinogens Gestation Female Pregnancy Complications Neoplastic |
| Zdroj: | Cancer Prevention Research. 6:1194-1211 |
| ISSN: | 1940-6215 1940-6207 |
| DOI: | 10.1158/1940-6207.capr-13-0207 |
| Popis: | Using a preclinical model, we investigated whether excess estradiol (E2) or leptin during pregnancy affects maternal mammary tumorigenesis in rats initiated by administering carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) on day 50. Two weeks later, rats were mated, and pregnant dams were treated daily with 10 μg of 17β-estradiol, 15 μg of leptin, or vehicle from gestation day 8 to 19. Tumor development was assessed separately during weeks 1 to 12 and 13 to 22 after DMBA administration, because pregnancy is known to induce a transient increase in breast cancer risk, followed by a persistent reduction. Parous rats developed less (32%) mammary tumors than nulliparous rats (59%, P < 0.001), and the majority (93%) of tumors in the parous rats appeared before week 13 (vs. 41% in nulliparous rats), indicating that pregnancy induced a transient increase in breast cancer risk. Parous rats exposed to leptin (final tumor incidence 65%) or E2 (45%) during pregnancy developed mammary tumors throughout the tumor-monitoring period, similar to nulliparous control rats, and the incidence was significantly higher in both the leptin- and E2-exposed dams after week 12 than in the vehicle-exposed parous dams (P < 0.001). The mammary glands of the exposed parous rats contained significantly more proliferating cells (P < 0.001). In addition, the E2- or leptin-treated parous rats did not exhibit the protective genomic signature induced by pregnancy and seen in the parous control rats. Specifically, these rats exhibited downregulation of genes involved in differentiation and immune functions and upregulation of genes involved in angiogenesis, growth, and epithelial-to-mesenchymal transition. Cancer Prev Res; 6(11); 1194–211. ©2013 AACR. |
| Databáze: | OpenAIRE |
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