RESUMO
The oncogenic effects of autocrine human growth hormone (hGH) have been intensively investigated in estrogen receptor-positive mammary carcinoma (ER + MC) cells. We demonstrated herein that autocrine hGH promoted cancer stem cell (CSC)-like properties of estrogen receptor-negative mammary carcinoma (ER-MC) cells in vitro. In xenograft studies, autocrine hGH increased the tumor initiating capacity of ER-MC cells. We also observed that autocrine hGH promoted migration and invasion of ER-MC cells in vitro, and metastasis in vivo. Thus, inhibition of hGH is a potential therapeutic strategy to prevent tumor initiation and metastasis of ER-MC.
Assuntos
Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Hormônio do Crescimento Humano/metabolismo , Células-Tronco Neoplásicas/patologia , Receptores de Estrogênio/metabolismo , Família Aldeído Desidrogenase 1 , Animais , Comunicação Autócrina , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hormônio do Crescimento Humano/biossíntese , Hormônio do Crescimento Humano/genética , Humanos , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Isoenzimas/biossíntese , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transplante de Neoplasias , RNA Mensageiro/biossíntese , Retinal Desidrogenase/biossíntese , Esferoides Celulares , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
OBJECTIVE: Alzheimer's disease (AD) is one of the major disorders worldwide. Recent research suggests that the amyloid-ß precursor protein intracellular domain (AICD) is a potential contributor to AD development and progression. The small AICD is rapidly degraded after processing from the full-length protein. The present study aimed to apply a highly efficient biotinylation approach in vitro to study AICD-associated complexes in neurocytes. METHODS: By co-expressing Escherichia coli biotin ligase with biotinyl-tagged AICD in the SH-SY5Y neuronal cell line, the effects of AICD overexpression on cell proliferation and apoptosis were analyzed. Besides, AICD-associated nuclear transcriptional complexes were purified and then examined by mass spectrometry. RESULTS: Our data showed that AICD overexpression not only affected cell proliferation but also led to apoptosis in differentiated SH-SY5Y cells. Moreover, biotinylation allowed single-step purification of biotinylated AICD-associated complexes from total nuclear extract via high-affinity biotin-streptavidin binding. Following this by mass spectrometry, we identified physically associated proteins, some reported previously and other novel binding partners, CUX1 and SPT5. CONCLUSION: Based on these results, a map of the AICD-associated nuclear interactome was depicted. Specifically, AICD can activate CUX1 transcriptional activity, which may be associated with AICD-dependent neuronal cell death. This work helps to understand the AICD-associated biological events in AD progression and provides novel insights into the development of AD.
