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1.
Cancer Lett ; 483: 66-74, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32142917

RESUMO

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5ß1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.

2.
Oncol Rep ; 41(3): 1901-1910, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747221

RESUMO

Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely used endocrine therapy for patients with ER­positive breast cancer. However, ~30% of tamoxifen­treated breast cancers do not initially respond to tamoxifen, and neither do they eventually develop tamoxifen resistance. Bcl­2­associated athanogene 1 (BAG­1) is a multifunctional protein that interacts with a wide range of molecules to protect cells from apoptosis otherwise induced by cytotoxic drugs, growth factor withdrawal, radiation and stress. The aim of the present study was to investigate the function of BAG­1 in tamoxifen resistance. Immunohistochemistry techniques were used to determine BAG­1 expression in 119 stage I­III primary breast cancer tissues and it was identified that BAG­1 was significantly overexpressed in ER­positive breast cancer (P=0.001). Knockdown of BAG­1 by short interfering RNA was revealed to downregulate ER, and upregulate phospho (p)­protein kinase B (Akt) and p­mammalian target of rapamycin (mTOR) levels. Furthermore, significantly decreased tamoxifen­induced apoptosis (41.70±1.93 vs. 55.03±2.39%; P=0.012) was observed in T47D cells following the silencing of BAG­1. In contrast, overexpression of BAG­1 long enhanced apoptosis (65.10±2.35 vs. 55.03±2.39%; P=0.039) in T47D cells treated with tamoxifen. Combination treatment of tamoxifen and an mTOR inhibitor restored the inhibitory effects of tamoxifen in T47D cells exhibiting low BAG­1 expression levels (66.87±2.27 vs. 57.07±2.46%; P=0.037). In conclusion, there results of the present study indicated that suppression of BAG­1 expression may activate the phosphoinositide 3­kinase/Akt/mTOR pathway and protect ER­positive breast cancer cells from tamoxifen­induced inhibition of proliferation. ER­positive breast cancer cells exhibiting low BAG­1 expression appeared to be more sensitive to treatment with the mTOR inhibitor rapamycin. Furthermore, the results indicated that combination treatment targeting ER with tamoxifen and targeting mTOR with rapamycin may significantly potentiate the inhibitory effect in BAG­1­silenced cells.


Assuntos
Proteínas de Ligação a DNA/genética , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Fatores de Transcrição/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Receptores Estrogênicos/genética , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia
3.
Nanoscale ; 10(9): 4406-4414, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29451567

RESUMO

We have developed a strategy for synthesizing immediately activable, water-soluble, compact (∼10-12 nm hydrodynamic diameter) quantum dots with a small number of stable and controllable conjugation handles for long distance delivery and subsequent biomolecule conjugation. Upon covalent conjugation with engineered monovalent streptavidin, the sample results in a population consisting of low-valency quantum dots. Alternatively, we have synthesized quantum dots with a small number of biotin molecules that can self-assemble with engineered divalent streptavidin via high-affinity biotin-streptavidin interactions. Being compact, stable and highly specific against biotinylated proteins of interest, these low-valency quantum dots are ideal for labeling and tracking single molecules on the cell surface with high spatiotemporal resolution for different biological systems and applications.

4.
Biotechnol Biofuels ; 8: 29, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25834637

RESUMO

BACKGROUND: Siberian apricot (Prunus sibirica L.) has emerged as a novel potential source of biodiesel in China, but the molecular regulatory mechanism of oil accumulation in Siberian apricot seed kernels (SASK) is still unknown at present. To better develop SASK oil as woody biodiesel, it is essential to profile transcriptome and to identify the full repertoire of potential unigenes involved in the formation and accumulation of oil SASK during the different developing stages. RESULTS: We firstly detected the temporal patterns for oil content and fatty acid (FA) compositions of SASK in 7 different developing stages. The best time for obtaining the high quality and quantity of SASK oil was characterized at 60 days after flowering (DAF), and the representative periods (10, 30, 50, 60, and 70 DAF) were selected for transcriptomic analysis. By Illumina/Solexa sequencings, approximately 65 million short reads (average length = 96 bp) were obtained, and then assembled into 124,070 unigenes by Trinity strategy (mean size = 829.62 bp). A total of 3,000, 2,781, 2,620, and 2,675 differentially expressed unigenes were identified at 30, 50, 60, and 70 DAF (10 DAF as the control) by DESeq method, respectively. The relationship between the unigene transcriptional profiles and the oil dynamic patterns in developing SASK was comparatively analyzed, and the specific unigenes encoding some known enzymes and transcription factors involved in acetyl-coenzyme A (acetyl-CoA) formation and oil accumulation were determined. Additionally, 5 key metabolic genes implicated in SASK oil accumulation were experimentally validated by quantitative real-time PCR (qRT-PCR). Our findings could help to construction of oil accumulated pathway and to elucidate the molecular regulatory mechanism of increased oil production in developing SASK. CONCLUSIONS: This is the first study of oil temporal patterns, transcriptome sequencings, and differential profiles in developing SASK. All our results will serve as the important foundation to further deeply explore the regulatory mechanism of SASK high-quality oil accumulation, and may also provide some reference for researching the woody biodiesel plants.

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