• Journal of Plant Biotechnology
• /
• 제46권3호
• /
• pp.217-227
• /
• 2019

Production of therapeutic monoclonal antibodies (mAbs) using a plant platform has been considered an alternative to the mammalian cell-based production system. A plant-derived mAb CO17-1AK ($mAb^P$ COK) can specifically bind to various types of cancer cell lines. The target protein of $mAb^P$ COK is the epithelial cell adhesion molecule (EpCAM) highly expressed in human epithelial cancer cells, including breast and colorectal cancer cells. It has been hypothesized that its overexpression supports tumor growth and metastasis. A ganglioside is extended well beyond the surfaces of the various cell membranes and has roles in cell growth, inflammation, differentiation, and carcinogenesis. However, the regulation of EpCAM gene expression in breast cancers and the role of gangliosides in oncogenesis are unclear. Here, the purpose of this study was to determine the effects of $mAb^P$ COK on human breast cancer cell proliferation, apoptosis, and ganglioside expression patterns. Our results show that treatment with $mAb^P$ COK suppressed the growth of breast cancer cells and induced apoptotic cell death. It also upregulated the expression of metastasis-related gangliosides in breast cancer cells. Thus, treatment with $mAb^P$ COK may have chemo-preventive therapeutic effects against human breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10245-10250
• /
• 2015

Background: Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. Materials and Methods: The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Results: Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Conclusions: Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

• BMB Reports
• /
• 제44권8호
• /
• pp.523-528
• /
• 2011

To identify novel genes that are regulated by promoter methylation, a combinational approach involving in silico mining followed by molecular assay was performed. From the expression microarray data registered in the European bioinformatics institute (EBI), genes showing downregulation in breast cancer cells were initially screened and then selected by e-Northern analysis using the Unigene database. A series of these in silico methods identified CAMK2B and ARFGEF1 as candidates, and the two genes were revealed to be hypermethylated in breast cancer cell lines and hypomethylated in normal breast cell lines. Additionally, cancer cell lines showed downregulated expression of these genes. Furthermore, treatment of the cancer cell lines with a demethylation agent, 5-Aza-2'-deoxycytidine, recovered expression of CAMK2B and ARFGEF1, implying that hypermethyaltion silenced gene activity in cancer cells. Taken together, promoter methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in breast cancer cell lines and can be utilized for the application to clinical cancer tissues.

• Molecules and Cells
• /
• 제39권3호
• /
• pp.258-265
• /
• 2016

In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.

• BMB Reports
• /
• 제52권2호
• /
• pp.113-118
• /
• 2019

The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권11호
• /
• pp.4623-4628
• /
• 2015

Breast cancer still remains as the most frequent cancer with second mortality rate in women worldwide. There are no validated biomarkers for detection of the disease in early stages with effective power in diagnosis and therapeutic approaches. Cancer/testis antigens are recently promising tumor antigens and suitable candidates for targeted therapies and generating cancer vaccines. We conducted the present study to analyze transcript changes of two cancer/testis antigens, OIP5 and TAF7L, in breast tumors and cell lines in comparison with normal breast tissues by quantitative real time RT-PCR for the first time. Significant over-expression of OIP5 was observed in breast tumors and three out of six cell lines including MDA-MB-468, T47D and SKBR3. Not significant expression of TAF7L was evident in breast tumors but significant increase was noted in three out of six cell lines including MDA-MB-231, BT474 and T47D. OIP5 has ssignificant role in chromatin organization and cell cycle control during cell cycle exit and normal chromosome segregation during mitosis and TAF7L is a component of the transcription factor IID, which is involved in transcription initiation of most protein coding genes. TAF7Lis located at X chromosome and belongs to the CT-X gene family of cancer/testis antigens which contains about 50% of CT antigens, including those which have been used in cancer immunotherapy.

• 한국환경성돌연변이발암원학회지
• /
• 제24권2호
• /
• pp.51-66
• /
• 2004

Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS). Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and west-ern bolt. In MCF-10A cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose- and time- dependent. T47-D cells treated with 1.0 $\muM$ tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 $\muM$ tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyelin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

• BMB Reports
• /
• 제56권7호
• /
• pp.410-415
• /
• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• Molecules and Cells
• /
• 제42권9호
• /
• pp.628-636
• /
• 2019

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권4호
• /
• pp.1725-1727
• /
• 2016

Breast cancer contributes to approximately 23% of the cancer cases identified and 14% of cancer related deaths worldwide. Including a strong association between genetic and environmental factors, breast cancer is a complex and multi factorial disorder. Two high penetration breast cancer susceptibility genes (BRCA1 and BRCA2) have been identified, and germ line mutations in these are thought to account for between 5% and 10% of all breast cancer cases. The human BRCA1 gene, located on 17q, is involved in the regulation of cell proliferation by aiding in DNA repair, transcriptional responses to DNA damage and cell cycle check points. Mutations in this gene enhance cell proliferation and facilitate formation of tumors. Two mutations, the 185 deletion of AG and the 4627 substitution from C to A, are founder mutations in the BRCA1 gene for breast cancer in Asian populations. Allele specific PCR was performed to detect these selected mutations in 120 samples. No mutation of 4627 C to A was detected in the samples and only one of the patients had the 185 del AG mutation in the heterozygous condition. Our collected samples had lower consanguinity and family history indicating the greater involvement of environmental as compared to genetic factors.