scholarly journals 111In-labeled trastuzumab-modified gold nanoparticles are cytotoxic in vitro to HER2-positive breast cancer cells and arrest tumor growth in vivo in athymic mice after intratumoral injection

2016 ◽  
Vol 43 (12) ◽  
pp. 818-826 ◽  
Author(s):  
Zhongli Cai ◽  
Niladri Chattopadhyay ◽  
Kaiyu Yang ◽  
Yongkyu Luke Kwon ◽  
Simmyung Yook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Intratumoral Injection ◽  
Athymic Mice ◽  
Her2 Positive ◽  
Positive Breast Cancer

scholarly journals A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Yan ◽  
Xiao Cheng ◽  
Lin Li ◽  
Rumeng Zhang ◽  
Yong Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Suppressive Effect ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Large Molecular Weight ◽  
Positive Breast Cancer

Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells in vitro. Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection in vivo. The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.

scholarly journals JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yanlin Ren ◽  
Dongyin Chen ◽  
Zurong Zhai ◽  
Junjie Chen ◽  
Aiping Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
E3 Ubiquitin Ligase ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

AbstractThe overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increased the ubiquitination of HER2 at the K716 site through the E3 ubiquitin ligase SMURF1 which was due to the decreased expression of NEDD4, the E3 ubiquitin ligase of SMURF1. In conclusion, JAC1 suppresses the proliferation of HER2-positive breast cancer cells through the JWA triggered HER2 ubiquitination signaling. JAC1 may serve as a potential therapeutic agent for HER2-positive breast cancer.

scholarly journals Oleanolic Acid’s Semisynthetic Derivatives HIMOXOL and Br-HIMOLID Show Proautophagic Potential and Inhibit Migration of HER2-Positive Breast Cancer Cells In Vitro

2021 ◽  
Vol 22 (20) ◽  
pp. 11273
Author(s):  
Natalia Magdalena Lisiak ◽  
Izabela Lewicka ◽  
Mariusz Kaczmarek ◽  
Jacek Kujawski ◽  
Barbara Bednarczyk-Cwynar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Approximately 20–30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes’ derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin β1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.

scholarly journals HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Hussain ◽  
Paromita Deb ◽  
Avisankar Chini ◽  
Monira Obaid ◽  
Arunoday Bhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Female Rats ◽  
Er Positive ◽  
Gene Regulatory ◽  
Cancer Tissues ◽  
Positive Breast Cancer

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

Identification of estrogenically synthesized LRP16 as an ERα coactivator and its role in ERα-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10676-10676
Author(s):  
W. Han ◽  
Y. Zhao ◽  
Z. Wu ◽  
Y. Mu ◽  
L. Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Northern Blot ◽  
Breast Cancer Cells ◽  
Tumor Diameter ◽  
Er Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

10676 Background: Aberrant ERα activity is linked to genesis and malignant progression of breast cancer through direct target gene activation or repression. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERα. LRP16 was identified previously to be an estrogen (E2) responsive gene, but its function involving in conferring estrogen signalling pathway is not clear. Methods: Endogenous LRP16 expression in MCF-7 cells was stably suppressed by retrovirus-mediated small interference RNA (siRNA). The effects of LRP16 expression on E2-stimulated growth and invasive ability of MCF-7 cells were determined in vitro and in vivo assays. The effects of LRP16 expression on ERα transactivation were determined by luciferase assays. The interaction of LRP16 and ERα was examined by GST pull-down and coimmunopricipitation (CoIP) assays. Northern blot and Western blot were used to detect the mRNA and protein levels of ER target genes in LRP16-inhibited MCF-7 cells. The LRP16 expression levels in primary breast cancer were detected by Northern blot. Results: Fristly, LRP16 expression was characterized to be dependent on estrogen activities. Then, LRP16 was identified to be an estrogen-independent ERα cofactor in ER-positive breast cancer cells and demonstrate that LRP16 is an essential coactivator to ERα-mediated transactivation in an estrogen-dependent manner. Suppression of LRP16 expression in ER-positive breast cancer cells specifically inhibits the transcription of ER upregulated genes, results in the increase of E-cadherin expression through ER mediation. In vitro and in vivo data demonstrate that suppression of LRP16 inhibits the ability of estrogen-stimulated proliferation and invasiveness of ER-positive breast cancer cells. The pathological and clinical characteristics of human breast cancer includining ER/PR-positiveness, tumor diameter and the involvement of axillary lymphoid nodes were tightly linked with the LRP16 gene expression level. Conclusions: These results establish a mechanistic link between estrogen receptor status, its coactivator LRP16, and progression of ER-positive breast cancers, and may provide a novel antiestrogenic target for the therapy of ER positive breast cancer. No significant financial relationships to disclose.

scholarly journals The synergistic antitumor effect of combined Anti-Human Epidermal Growth Factor Receptor 2 (HER2) antibody and Gamma Interferon therapy to Ab resistant breast cancer cells

2019 ◽  
Author(s):  
Toshihiko Gocho ◽  
Hiromichi Tsuchiya ◽  
Shotaro Kamijo ◽  
Yoshitaka Yamazaki ◽  
Yui Akita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Combined Therapy ◽  
Her2 Positive ◽  
Ifn Γ ◽  
Positive Breast Cancer

AbstractAnti-HER2 antibody is molecular targeted antibody for cancer therapy. Approximately 20% of breast cancers are characterized by overexpression of HER2 protein. However, the recurrence rate was 30% and the metastasis rate was 18% one year after treatment of Anti-HER2 antibody for HER2 positive breast cancer. The resistance to antibody treatment is a major problem for patients. We previously reported that Anti-HER2 antibody and Gamma Interferon (IFN-γ) combined therapy showed higher anti-tumor effect than usual therapy in vitro and in vivo mouse experiments.In this study, we evaluated whether anti-HER2 antibody and IFN-γ combined therapy shows good synergistic effect against drug resistant HER2 positive breast cancer cells and higher antitumor effect than conventional clinical treatment. The resistant cell lines were made under the continuous presence of antibody until cell growth was not affected by the drug. We divided the resistant cells into the appropriate number of groups, which we and treated with anti-cancer therapy. We evaluated the antitumor effect for both in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. And we investigated the differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues, especially related to immunity system.The combined therapy showed significantly higher anti-tumor effect than other groups in vitro and in vivo experiments. The combined therapy affects anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 antibody resistant breast cancer, helping patients suffering from cancer progression after developing treatment resistance.

scholarly journals The Agonist of JWA Gene JAC1 Suppresses Proliferation of Breast Cancer Through the JWA/p38/SMURF1/HER2 Signaling

2020 ◽  
Author(s):  
Yanlin Ren ◽  
Dongyin Chen ◽  
Junjie Chen ◽  
Zurong Zhai ◽  
Aiping Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
E3 Ubiquitin Ligase ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Her2 Signaling ◽  
Positive Breast Cancer

Abstract Background The overexpression of HER2 is associated with malignant proliferation and invasiveness in breast cancer. Although HER2-targeting drugs have been clinically applied for cancer treatment, none of them could reduce overexpressed HER2. In this study, we reported that JAC1 could suppress proliferation of breast cancer cells via degrading HER2. Methods JWA-HER2 association was analyzed by IHC in 90 paired cases of breast cancer and adjacent non-cancerous tissues. Regulatory effect of JAC1, the agonist of JWA gene, on HER2-positive breast cancer cells was studied using colony formation assay. The effect of JAC1 on the localization of HER2 was detected by immunofluorescence microscopy assay. Western blotting, RT-PCR and immunoprecipitation assay were utilized to investigate the mechanisms of JWA on regulating HER2. Finally, xenograft mouse models were established in nude mice using BT474 cells to confirm the effect of JAC1 in vivo. Results JAC1, a small molecule agonist of JWA gene, dose-dependently suppressed proliferation in HER2-positive breast cancer in vitro and in vivo through degrading HER2. The mechanistic evidences showed that JAC1 increased the ubiquitination of HER2 at the K716 through the E3 ubiquitin ligase SMURF1. Furthermore, SMURF1 was activated due to reduced expression of NEDD4, an E3 ubiquitin ligase for SMURF1 through the JWA-p38-GATA-1-NEDD4 axis. Conclusions JAC1 suppresses the proliferation in HER2-positive breast cancer through the JWA/p38/GATA-1/NEDD4/SMURF1/HER2 signaling. JAC1 may serve as a novel therapeutic agent to breast cancer.

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