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PLoS One ; 16(8): e0255701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34358244

RESUMO

Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prolactina/farmacologia , Receptores da Prolactina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma Epitelial do Ovário/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Células MCF-7 , Neoplasias Ovarianas/patologia , Fosforilação/efeitos dos fármacos , Intervalo Livre de Progressão , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores da Prolactina/genética , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Taxa de Sobrevida
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