Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain

Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

doi:10.3390/ijms161126024

Cited by 44 publications

(30 citation statements)

References 100 publications

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“…Moreover, these pluripotency transcription factors are present in breast stem cells and help to maintain an undifferentiated state (38). However, in breast cancer stem cells pluripotency transcription factors are overexpressed (39, 55, 56), which suggests the hypothesis that “aberrant expression of OCT4, SOX2 and NANOG causes continuous activation of self-renewal leading to oncogenic transformation and tumor initiation and maintenance” (37). For example, SOX2 is overexpressed in gliomas and has an essential role in the initiation, maintenance and recurrence of tumors (37, 59, 60).…”

Section: Discussionmentioning

confidence: 99%

“…However, in breast cancer stem cells pluripotency transcription factors are overexpressed (39, 55, 56), which suggests the hypothesis that “aberrant expression of OCT4, SOX2 and NANOG causes continuous activation of self-renewal leading to oncogenic transformation and tumor initiation and maintenance” (37). For example, SOX2 is overexpressed in gliomas and has an essential role in the initiation, maintenance and recurrence of tumors (37, 59, 60). Similarly, SOX2 is overexpressed in breast carcinomas (37, 61), and in particular, in breast cancer stem cells relative to bulk tumor cells (39).…”

Section: Discussionmentioning

confidence: 99%

“…For example, SOX2 is overexpressed in gliomas and has an essential role in the initiation, maintenance and recurrence of tumors (37, 59, 60). Similarly, SOX2 is overexpressed in breast carcinomas (37, 61), and in particular, in breast cancer stem cells relative to bulk tumor cells (39). In this study, we showed that SOX2 expression can be induced in MCF-7 mammospheres treated with 10 nM BPA.…”

Section: Discussionmentioning

confidence: 99%

“…The transcription factors OCT4, SOX2 and NANOG, which are master regulators of pluripotency in embryonic stem cells (35–37), are also present in breast stem cells and function to maintain an undifferentiated state and to prevent differentiation (37, 38). Of these factors, SOX2 is the only one detectable by immunohistochemical staining of breast tumors or mammospheres (39).…”

Section: Introductionmentioning

confidence: 99%

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Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells

et al. 2017

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Bisphenol A (BPA) is an endocrine disrupting compound used in food and beverage plastic containers, and has been shown to increase breast cancer cellular proliferation. However, the concentrations of BPA used in these experiments is far higher than the physiological levels of BPA detected in the human body. We observed in vitro that exposure of MCF-7 cells to physiological concentrations of BPA failed to increase cell proliferation or to induce canonical estrogen-responsive genes (pS2 and progesterone receptor, PR), in contrast to 17β-estradiol (E2) treatment. However, MCF-7 cells treated with 10 nM BPA induced ALDH1 expression, a marker of human mammary stem cells. When treated with 10 nM BPA, mammospheres derived either from MCF-7 cells, a patient-derived xenograft or the normal mouse mammary gland, exhibited increased size; however, these effects were not observed in MDA-MB-231 mammospheres. Mechanistically, BPA induced SOX2 mRNA and protein in MCF-7 mammospheres, resulting from enhanced CREB phosphorylation, and subsequent binding of pCREB to a SOX2 downstream enhancer. These findings suggest that physiological levels of BPA increase ER+ breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells

et al. 2017

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“…Mammary stem cells are pluripotent in nature playing a role in tissue repair and regeneration [72]. Studies suggest the origin of mammary stem cells in adult stage is from the proliferating embryonic stem cells of the mammary gland during embryogenesis which has become quiescent in the adult stage [73].…”

Section: Asian J Pharm Clin Resmentioning

confidence: 99%

New Insights of Mammary Gland During Different Stages of Development

Jena

Mohanty

2017

Asian J Pharm Clin Res

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Mammary gland is a unique organ with its function of milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells proliferate, differentiate, undergo apoptosis, and tissue remodeling following a cyclic pathway in lactation -involutionlactation cycle, thus fine tuning the molecular events through hormones, and regulatory molecules. Several studies are performed on the mammary gland development, lactogenesis, and involution process in molecular details. The developmental stages of mammary gland are embryonic, prepubertal, pubertal, pregnancy, lactation, and involution. Major developmental processes occur after puberty with hormones and growth factors playing crucial role. The two major pathways such as Janus kinases-signal transducer and activator of transcription pathway and PI3K-Akt pathway play a major role in maintaining the lactation. The involution process is a well-orchestrated event involving several signaling molecules and making the gland ready for subsequent lactation. The review focuses on findings with molecular details of different stages of the mammary gland development and signaling pathways involved in lactation-involution cycle. Deep insight into the developmental stages of mammary gland will pave the way to understand mammary gland biology, apoptosis, oncogenesis, and it will help the researchers to use mammary gland as a model for research on various aspects.

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Targeting AMP‐activated kinase impacts hepatocellular cancer stem cells induced by long‐term treatment with sorafenib

et al. 2019

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Hepatocellular carcinoma ( HCC ) is the third leading cause of cancer death worldwide. HCC treatment is hindered by the frequent emergence of chemoresistance to the multikinase inhibitor sorafenib, which has been related to the presence of cancer stem cells ( CSC s) that self‐renew and often escape therapy. The key metabolic sensor AMP ‐activated kinase ( AMPK ) has recently been recognized as a tumour growth regulator. In this study, we aimed to elucidate the role of AMPK in the development of a stem cell phenotype in HCC cells. To this end, we enriched the CSC population in HCC cell lines that showed increased expression of drug resistance ( ALDH 1A1, ABCB 1A) and stem cell ( CD 133, Nanog, Oct4, alpha fetoprotein) markers and demonstrated their stemness phenotype. These cells were refractory to sorafenib‐induced cell death. We report that sorafenib‐resistant cells had lower levels of total and phosphorylated AMPK as well as its downstream substrate, ACC , compared with the parental cells. Interestingly, AMPK knockdown with si RNA or inhibition with dorsomorphin increased the expression of stem cell markers in parental cells and blocked sorafenib‐induced cell death. Conversely, the upregulation of AMPK , either by transfection or by pharmacological activation with A‐769662, decreased the expression of ALDH 1A1, ABCB 1A, CD 133, Nanog, Oct4, and alpha fetoprotein, and restored sensitivity to sorafenib. Analysis of the underlying mechanism points to hypoxia‐inducible factor HIF ‐1α as a regulator of stemness. In vivo studies in a xenograft mouse model demonstrated that stem‐like cells have greater tumourigenic capacity. AMPK activation reduced xenograft tumour growth and decreased the expression of stem cell markers. Taken together, these results indicate that AMPK may serve as a novel target to overcome chemoresistance in HCC .

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Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain

Cited by 44 publications

References 100 publications

Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells

Bisphenol A Induces Sox2 in ER+ Breast Cancer Stem-Like Cells

New Insights of Mammary Gland During Different Stages of Development

Targeting AMP‐activated kinase impacts hepatocellular cancer stem cells induced by long‐term treatment with sorafenib

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