{"id":"CONICETDig_67f96ab822408b13a2f98aedd081e4ec","dc:title":"Efectos de la T4 en la apoptosis y proliferaci\u00f3n de tumores de mama","dc:creator":"Zyla, Leila Ester","dc:date":"2024","dc:description":["Hypothyroidism is a protective factor against breast cancer but long-term exposure or overdoses of thyroid replacement therapy with thyroxine (T4) may increase breast cancer risk. Objective: to study, in vivo and in vitro, the effects of T4 on the proliferation and apoptosis of mammary tumors of hypo- and euthyroid rats, and the possible mechanisms involved in these effects. Material and Methods: Female Sprague-Dawley rats were treated with a single dose of dimethylbenzathracene (15 mg\/rat) at 55 days of age and were divided into three groups: hypothyroidism (HypoT; 0.01% 6-N-propyl-2-thiouracil -PTU- in drinking water, n = 20), hypothyroidism treated with T4 (HypoT + T4; 0.01% PTU in drinking water and 0.25 mg\/kg\/day T4 via sc; n = 20) and EUT (untreated control, n = 20). At sacri\ufb01ce, tumor explants from HypoT and EUT rats were obtained and treated either with 10 10 M T4 in DMEM\/F12 without phenol red with 1% Charcoalized Fetal Bovine Serum or DMEM\/ F12 only for 15 min to evaluate intracellular signaling pathways associated with T4, and 24 h to evaluate changes in the expression of hormone receptors and proteins related to apoptosis and proliferation by immunohisto-chemistry and Western Blot. Results: In vivo, hypothyroidism retards mammary carcinogenesis but its treatment with T4 reverted the protective effects. In vitro, the proliferative and anti-apoptosis mechanisms of T4 were different regarding the thyroid status. In EUT tumors, the main signaling pathway involved was the cross-talk with other receptors, such as ER\u03b1, PgR, and HER2. In HypoT tumors, the non-genomic signaling pathway of T4 was the chief mechanism involved since \u03b1v\u03b23 integrin, HER2, \u03b2-catenin and, downstream, PI3K\/AKT and ERK signaling pathways were activated. Conclusion: T4 can regulate mammary carcinogenesis by mainly activating its non-genomic signaling pathway and by interacting with other hormone or growth factor pathways endorsing that overdoses of thyroid replacement therapy with T4 can increase the risk of breast cancer."],"dc:format":["application\/octet-stream"],"dc:language":["eng"],"dc:type":"dataset","dc:rights":["info:eu-repo\/semantics\/restrictedAccess","Protecci\u00f3n de datos personales (Ley 25.326)"],"dc:relation":["info:eu-repo\/grantAgreement\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas. Centro Cient\u00edfico Tecnol\u00f3gico Conicet - Mendoza\/","info:eu-repo\/grantAgreement\/\/"],"dc:identifier":"https:\/\/repositoriosdigitales.mincyt.gob.ar\/vufind\/Record\/CONICETDig_67f96ab822408b13a2f98aedd081e4ec"}