Endocrine and Cell Surface Receptor Signaling in Breast Carcinogenesis

Alanazi, Ibrahim O.; Khan, Zahid

doi:10.5772/intechopen.74679

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…As a result, Notch intracellular domain (NICD) is released and translocated to the nucleus forming a complex with transcription factor CSL and transcriptional coactivators including mastermind-like polypeptides (MAML) and recombination signal binding protein for immunoglobulin kappa J region (RBPj). is interaction leads to the activation of various target genes associated with cell survival, differentiation, cell growth, and tumorigenesis [18].…”

Section: Introductionmentioning

confidence: 99%

Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome

Shaik

Alanazi

Pathan

et al. 2020

Journal of Oncology

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Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer stem cells that can invariably resist existing chemotherapeutic regimens. Notch signaling pathway has been involved in the maintenance of stem cells besides being crucial in cell fate decision and embryonic development. This pathway has also been implicated in several human malignancies including colorectal cancer. We investigated mRNA expression of four Notch receptors (Notch1–4), five ligands (Jag1, Jag2, Dll1, Dll3, and Dll4), and four target genes (Hes1, Hes5, Hey1, and Hey2) using highly specific TaqMan gene expression assays in colorectal adenomas and cancers. Upregulated expression of Notch receptors ranged between 29 and 73% in colorectal cancers and between 11 and 56% in adenomas. Expression of Notch3 and Notch4 receptors was significantly higher in colorectal cancers compared to normal and adenoma tissues. The Jagged and Delta-like ligands were overexpressed between 25 and 52% in colorectal cancers, while in adenomas, it ranged between 0 and 33%. Combining the data for upregulation of receptors and ligands suggests that 86% colorectal cancers and 56% adenomas exhibited overexpression of Notch pathway genes in our cohort. Notch target genes were upregulated between 24 and 33% in colorectal cancers and between 11 and 22% in adenomas. Collating upregulation of Notch receptors and ligands with the target genes showed concordance in 58% colorectal tumors. Additionally, we evaluated expression of Notch receptors, ligands, and target genes with prognosis using the TCGA mRNA expression dataset. Patients overexpressing Notch3, Notch4, and Hey1 had significantly poorer overall survival relative to those having lower levels of these genes. Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of colorectal cancers.

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Section: Introductionmentioning

confidence: 99%

Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome

Shaik

Alanazi

Pathan

et al. 2020

Journal of Oncology

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“…The signaling discrepancies between the two breast cancer cell lines might be associated with distinctive molecular profile including receptor status [70]. Indeed, BT-474 and MCF-7 cells have been known to exert different clinical responses to the same treatment [71].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Osthole on Human Breast Cancer Cell Progression via Induction of Cell Cycle Arrest, Mitochondrial Dysfunction, and ER Stress

2019

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Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Although, recently, the number of pathological studies of breast cancer have increased, it is necessary to identify a novel compound that targets multiple signaling pathways involved in breast cancer. Methods: The effects of osthole on cell viability, apoptosis, mitochondria-mediated apoptosis, production of reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress proteins of BT-474 and MCF-7 breast cancer cell lines were investigated. Signal transduction pathways in both cells in response to osthole were determined by western blot analyses. Results: Here, we demonstrated that osthole inhibited cellular proliferation and induced cell cycle arrest through modulation of cell cycle regulatory genes in BT-474 and MCF-7 cells. Additionally, osthole induced loss of mitochondrial membrane potential (MMP), intracellular calcium imbalance, and ER stress. Moreover, osthole induced apoptosis by activating the pro-apoptotic protein, Bax, in both cell lines. Osthole regulated phosphorylation of signaling proteins such as Akt and ERK1/2 in human breast cancer cells. Furthermore, osthole-induced activation of JNK protein-mediated apoptosis in both cell lines. Conclusions: Collectively, the results of the present study indicated that osthole may ameliorate breast cancer and can be a promising therapeutic agent for treatment of breast cancer.

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“…2-BOA may promote ER signaling by binding to ERα or ERβ, activating the protein downstream involved in the RAS/RAF, PI3K, and AKT signaling pathway. The activation of these signaling pathways modulates the cell cycle, cell growth, apoptosis, DAN repair, or angiogenesis, which is responsible for cancer progression (4,(21)(22)(23)(24). 2-BOA may also promote ER dimerization, which affects the transcriptional regulation of cancer-related target genes (24,25).…”

Section: Boa Identified In Acanthus Ilicifoliusmentioning

confidence: 99%

2-Benzoxazolinone as Breast Cancer Cells Inhibitor via Estrogen Receptor

Asrining Dhiani,

Ismail,

Subhan Maruf

et al. 2023

Curr. Trends Biotechnol. Pharm.

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Estrogen receptors alpha (ERα) and beta (ERβ) is highly expressed in different cancer cells. Inhibition of ERs by small molecules is a promising approach to developing novel anticancer agents amidst increased endocrine therapy resistance. A heterocyclic molecule, 2-benzoxazolinone (2-BOA) and its derivatives, found in Acanthus ilicifolius leaves, possesses anticancer on varied cancer cell types such as HeLa, MCF-7, A-549, and SW-480. However, the mechanism of its cancer cell growth inhibition is an enigma. This study aimed to unmask the activity of 2-BOA to inhibit the growth of the MCF-7 breast cancer cell line via estrogen receptors. The modulation mechanism was predicted by docking molecular of 2-BOA toward ERα (PDB ID: 2JF9) and ERβ (PDB ID: 5TOA). Subsequently, the MCF-7 cell viability assay was performed to validate the in-silico prediction. We preliminary identified the presence of 2-BOA in Acanthus ilicifolius leaves using high-performance liquid chromatography (HPLC). The binding energy of 2-BOA on ERα and ERβ exhibited a similar score (-6.3 kcal/mol). 2-BOA showed inhibition toward the MCF-7 breast cancer cell line with IC50 value 35.4 µM. 2-BOA may be a potent small molecule inhibitor of the MCF-7 breast cancer cell growth via estrogen receptors

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Endocrine and Cell Surface Receptor Signaling in Breast Carcinogenesis

Cited by 6 publications

References 46 publications

Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome

Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome

Inhibitory Effects of Osthole on Human Breast Cancer Cell Progression via Induction of Cell Cycle Arrest, Mitochondrial Dysfunction, and ER Stress

2-Benzoxazolinone as Breast Cancer Cells Inhibitor via Estrogen Receptor

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