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2 results on '"PTEN FUNCTION"'

1. The role of the PTEN/mTOR axis in clinical response of rectal cancer patients

Author

Oya Orun, Sevgi Özden, Olca Kılınç, Pınar Mega Tiber, Pelin Yonar, Zerrin Özgen, Hazan Özyurt, and Orun O., Özden S., Kılınç O., Mega Tiber P., Yonar P., Özgen Z., Özyurt H.

Subjects
p53, PTEN FUNCTION, EXPRESSION, PTEN, GENETİK VE KALITIM, BNIP3, NOXA, Life Sciences (LIFE), Molecular Biology and Genetics, Sağlık Bilimleri, Tıbbi Genetik, POOR-PROGNOSIS, Yaşam Bilimleri, Health Sciences, Genetics, PROGNOSTIC ROLE, Humans, Genetik, GENETICS & HEREDITY, MUTATION, Molecular Biology, Moleküler Biyoloji ve Genetik, MTOR INHIBITOR, Internal Medicine Sciences, Moleküler Biyoloji, Rectal Neoplasms, Temel Bilimler, TOR Serine-Threonine Kinases, REDD1, PTEN Phosphohydrolase, Life Sciences, Dahili Tıp Bilimleri, General Medicine, GENE, Tıp, MOLECULAR BIOLOGY & GENETICS, Yaşam Bilimleri (LIFE), Rectum cancer, E3 UBIQUITIN LIGASE, mTOR, Medicine, Tumor Suppressor Protein p53, Natural Sciences, Medical Genetics, Proto-Oncogene Proteins c-akt, mLST8, Signal Transduction
Abstract

© 2022, The Author(s), under exclusive licence to Springer Nature B.V.Background: Preoperative chemoradiotherapy has long been accepted as a method to improve survival and lifetime quality of rectal cancer patients. However, physiologic effects of these therapies largely depend on the resistance of cells to the radiation, type of chemotherapeutic agents and individual responses. As one of the signaling cascades involved in chemo- or radiation- resistance, the present study focused on several proteins involved in pTEN/Akt/mTOR pathway to explore their prognostic significance. Materials and methods: Samples from advanced stage rectal cancer patients were analyzed to detect expression levels of pTEN/Akt/mTOR pathway related proteins pTEN, mLST8, REDD1, BNIP3, SAG and NOXA, together with p53, by RT-qPCR. Kaplan–Meier analysis was used to assess expression-survival relation and correlations among all proteins and clinicopathological features were statistically analyzed. Results.: Except p53, none of the proteins showed prognostic significance. High p53 expression presented clear impact on overall survival and disease free survival. It was also significantly related to pathologic complete response. p53 showed high correlation to local recurrence as well. On the other hand, strong correlation was observed with PTEN expression and tumor response, but not with survival. High associations were also observed between mLST8/REDD1, PTEN and NOXA, confirming their role in the same cascade. Conclusion: The contentious role of p53 as a prognostic biomarker in colorectal cancer was further affirmed, while PTEN and REDD1 could be suggested as potential candidates. Additionally, NOXA emerges as a conjunctive element for different signaling pathways.

Published
2022

2. PTEN regulates retinal interneuron morphogenesis and synaptic layer formation

Author

Sakagami, Kiyo, Chen, Bryan, Nusinowitz, Steven, Wu, Hong, and Yang, Xian-Jie

Subjects
*PTEN protein, *PHOSPHATASES, *INTERNEURONS, *MORPHOGENESIS -- Molecular aspects, *LIPIDS, *RETINA, *RETINAL ganglion cells, *PHOTORECEPTORS
Abstract

Abstract: The lipid phosphatase PTEN is a critical negative regulator of extracellular signal-induced PI3K activities, yet the roles of PTEN in the neural retina remain poorly understood. Here, we investigate the function of PTEN during retinal development. Deletion of Pten at the onset of neurogenesis in retinal progenitors results in the reduction of retinal ganglion cells and rod photoreceptors, but increased Müller glial genesis. In addition, PTEN deficiency leads to elevated phosphorylation of Akt, especially in the developing inner plexiform layer, where high levels of PTEN are normally expressed. In Pten mutant retinas, various subtypes of amacrine cells show severe dendritic overgrowth, causing specific expansion of the inner plexiform layer. However, the outer plexiform layer remains relatively undisturbed in the Pten deficient retina. Physiological analysis detects reduced rod function and augmented oscillatory potentials originating from amacrine cells in Pten mutants. Furthermore, deleting Pten or elevating Akt activity in individual amacrine cells is sufficient to disrupt dendritic arborization, indicating that Pten activity is required cell autonomously to control neuronal morphology. Moreover, inhibiting endogenous Akt activity attenuates inner plexiform layer formation in vitro. Together, these findings demonstrate that suppression of PI3K/Akt signaling by PTEN is crucial for proper neuronal differentiation and normal retinal network formation. [Copyright &y& Elsevier]

Published
2012
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