Effects of Oral Contraceptives or a Gonadotropin-Releasing Hormone Agonist on Ovarian Carcinogenesis in Genetically Engineered Mice

Autor: Thomas Krausz, Keeley L. Mui, Woo Seok Lee, Melissa Gilliam, Sujatha Jagadeeswaran, Daniela M. Dinulescu, Ilyssa O. Gordon, Iris L. Romero, Helen H. Kim, Ernst Lengyel
Rok vydání: 2009
Předmět:
Cancer Research
Apoptosis
Gonadotropin-releasing hormone
Ethinyl Estradiol
Gonadotropin-Releasing Hormone
Immunoenzyme Techniques
Pathogenesis
Mice
Tumor Cells
Cultured
Mice
Knockout
Ovarian Neoplasms
education.field_of_study
Obstetrics and Gynecology
General Medicine
Contraceptives
Oral
Synthetic
Oncology
Matrix Metalloproteinase 2
Female
Agonist
medicine.medical_specialty
medicine.drug_class
Blotting
Western
Population
Mice
Transgenic
Biology
Placebo
Article
Proto-Oncogene Proteins p21(ras)
Gonadotropin-releasing hormone agonist
Internal medicine
medicine
Humans
Animals
PTEN
Neoplasm Invasiveness
education
Integrases
business.industry
PTEN Phosphohydrolase
Estrogens
medicine.disease
Disease Models
Animal
Endocrinology
Estrogen
biology.protein
Macaca
Norethindrone
business
Ovarian cancer
Chickens
Gonadotropins
Hormone
Zdroj: Cancer Prevention Research. 2:792-799
ISSN: 1940-6215
1940-6207
DOI: 10.1158/1940-6207.capr-08-0236
Popis: Although epidemiologic evidence for the ability of combined oral contraception (OC) to reduce the risk of ovarian cancer (OvCa) is convincing, the biological mechanisms underlying this effect are largely unknown. We conducted the present study to determine if OC also influences ovarian carcinogenesis in a genetic mouse model and, if so, to investigate the mechanism underlying the protective effect. LSL-K-rasG12D/+PtenloxP/loxP mice were treated with ethinyl estradiol plus norethindrone, contraceptive hormones commonly used in combined OC, or norethindrone alone, or a gonadotropin-releasing hormone agonist. The combined OC had a 29% reduction in mean total tumor weight compared with placebo (epithelial tumor weight, −80%). Norethindrone alone reduced mean total tumor weight by 42% (epithelial tumor weight, −46%), and the gonadotropin-releasing hormone agonist increased mean total tumor weight by 71% (epithelial tumor weight, +150%). Large variations in tumor size affected the P values for these changes, which were not statistically significant. Nonetheless, the OC reductions are consistent with the epidemiologic data indicating a protective effect of OC. Matrix metalloproteinase-2 activity was decreased in association with OC, indicating that OC may affect ovarian carcinogenesis by decreasing proteolytic activity, an important early event in the pathogenesis of OvCa. In contrast, OC increased invasion in a K-ras/Pten OvCa cell line established from the mouse tumors, suggesting that OC hormones, particularly estrogen, may have a detrimental effect after the disease process is under way. Our study results support further investigation of OC effects and mechanisms for OvCa prevention.
Databáze: OpenAIRE
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