scholarly journals Doxycycline Attenuates Atrial Remodeling by Interfering with MicroRNA-21 and Downstream Phosphatase and Tensin Homolog (PTEN)/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway

2018 ◽  
Vol 24 ◽  
pp. 5580-5587 ◽  
Author(s):  
Kai Zhang ◽  
Linru Zhao ◽  
Zuowang Ma ◽  
Weiding Wang ◽  
Xiongfeng Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Atrial Remodeling ◽  
Pi3k Signaling ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pi3k Signaling Pathway ◽  
Phosphoinositide 3 Kinase

scholarly journals Modeling PTEN overexpression-induced microcephaly in human brain organoids

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Navroop Dhaliwal ◽  
Wendy W.Y. Choi ◽  
Julien Muffat ◽  
Yun Li
Keyword(s):  
Human Brain ◽  
Human Genetics ◽  
Negative Regulator ◽  
Akt Inhibitor ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pi3k Signaling Pathway ◽  
Brain Organoid ◽  
Phosphoinositide 3 Kinase

AbstractThe phosphatase and tensin homolog (PTEN) protein, encoded by the PTEN gene on chromosome 10, is a negative regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway. Loss of PTEN has been linked to an array of human diseases, including neurodevelopmental disorders such as macrocephaly and autism. However, it remains unknown whether increased dosage of PTEN can lead to human disease. A recent human genetics study identifies chromosome 10 microduplication encompassing PTEN in patients with microcephaly. Here we generated a human brain organoid model of increased PTEN dosage. We showed that mild PTEN overexpression led to reduced neural precursor proliferation, premature neuronal differentiation, and the formation of significantly smaller brain organoids. PTEN overexpression resulted in decreased AKT activation, and treatment of wild-type organoids with an AKT inhibitor recapitulated the reduced brain organoid growth phenotypes. Together, our findings provide functional evidence that PTEN is a dosage-sensitive gene that regulates human neurodevelopment, and that increased PTEN dosage in brain organoids results in microcephaly-like phenotypes.

scholarly journals FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination

2012 ◽  
Vol 209 (2) ◽  
pp. 395-406 ◽  
Author(s):  
Alabbas Alkhatib ◽  
Markus Werner ◽  
Eva Hug ◽  
Sebastian Herzog ◽  
Cathrin Eschbach ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Rearrangement ◽  
B Cell Development ◽  
Mrna Splicing ◽  
Pi3k Signaling ◽  
Immunoglobulin Gene ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Vh Genes ◽  
Phosphoinositide 3 Kinase

Somatic rearrangement of immunoglobulin (Ig) genes is a key step during B cell development. Using pro–B cells lacking the phosphatase Pten (phosphatase and tensin homolog), which negatively regulates phosphoinositide-3-kinase (PI3K) signaling, we show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression. Interestingly, FoxO1 did not influence Ikaros transcription; instead, FoxO1 is essential for proper Ikaros mRNA splicing, as FoxO1-deficient cells contain aberrantly processed Ikaros transcripts. Moreover, FoxO1-induced Ikaros expression was sufficient only for proximal VH to DJH gene rearrangement. Simultaneous expression of the transcription factor Pax5 was needed for the activation of distal VH genes; however, Pax5 did not induce any Ig gene rearrangement in the absence of Ikaros. Together, our results suggest that ordered Ig gene rearrangement is regulated by distinct activities of Ikaros, which mediates proximal VH to DJH gene rearrangement downstream of FoxO1 and cooperates with Pax5 to activate the rearrangement of distal VH genes.

Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

2017 ◽  
Vol 24 (13) ◽  
Author(s):  
Safieh Ebrahimi ◽  
Mina Hosseini ◽  
Soodabeh Shahidsales ◽  
Mina Maftouh ◽  
Gordon A. Ferns ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Pi3k Signaling ◽  
Pi3k Signaling Pathway

scholarly journals BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells

2020 ◽  
Vol 15 (1) ◽  
pp. 501-510
Author(s):  
Bin Ma ◽  
Wenjia Guo ◽  
Meihui Shan ◽  
Nan Zhang ◽  
Binlin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Nuclear Localization ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
T47d Cells ◽  
Pi3k Signaling Pathway ◽  
Hormone Sensitive

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

scholarly journals Esthetic and Functional Improvement of Asymmetric Lower Limb Overgrowth in a Proteus Syndrome Patient: a Combined Surgical Technique

2021 ◽  
Author(s):  
Francesca Riccardi ◽  
Simone Catapano ◽  
Giuseppe Cottone ◽  
Dino Zilio ◽  
Luca Vaienti
Keyword(s):  
Adipose Tissue ◽  
Lower Limb ◽  
Vascular Malformations ◽  
Functional Improvement ◽  
Proteus Syndrome ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Genetic Mosaicism ◽  
Phosphoinositide 3 Kinase ◽  
The Right

AbstractProteus syndrome is a rare, sporadic, congenital syndrome that causes asymmetric and disproportionate overgrowth of limbs, connective tissue nevi, epidermal nevi, alteration of adipose tissue, and vascular malformations. Genetic mosaicism, such as activating mutations involving protein kinase AKT1, phosphoinositide 3 kinase (PI3-K), and phosphatase and tensin homolog (PTEN), may be important causes of Proteus syndrome. However, many patients have no evidence of mutations in these genes. Currently, the diagnosis is clinical and based on phenotypic features. This article reports a case of Proteus syndrome in a 14-year-old female patient who presented with linear epidermal nevi, viscera anomalies, and adipose tissue dysregulation. She showed an asymmetric progressive overgrowth of the right lower limb after birth bringing relevant functional and esthetic consequences. Therefore, she asked a plastic surgery consultation and a surgical treatment with a combined technique was planned. With our approach, we were able to reduce leg diameter and improve joint mobility reliably and safely with satisfying esthetic results.

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