PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation
Abstract
Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RAmore »
- Authors:
-
- Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)
- Publication Date:
- OSTI Identifier:
- 22210165
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 424; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; DNA; INFANTS; INHIBITION; MONOCLINIC LATTICES; NEOPLASMS; RECEPTORS; RETINOIC ACID; THERAPY
Citation Formats
Qiao, Jingbo, Paul, Pritha, Lee, Sora, Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, Qiao, Lan, Josifi, Erlena, Tiao, Joshua R., Chung, Dai H., E-mail: dai.chung@vanderbilt.edu, and Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation. United States: N. p., 2012.
Web. doi:10.1016/J.BBRC.2012.06.125.
Qiao, Jingbo, Paul, Pritha, Lee, Sora, Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, Qiao, Lan, Josifi, Erlena, Tiao, Joshua R., Chung, Dai H., E-mail: dai.chung@vanderbilt.edu, & Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation. United States. https://doi.org/10.1016/J.BBRC.2012.06.125
Qiao, Jingbo, Paul, Pritha, Lee, Sora, Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, Qiao, Lan, Josifi, Erlena, Tiao, Joshua R., Chung, Dai H., E-mail: dai.chung@vanderbilt.edu, and Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232. 2012.
"PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation". United States. https://doi.org/10.1016/J.BBRC.2012.06.125.
@article{osti_22210165,
title = {PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation},
author = {Qiao, Jingbo and Paul, Pritha and Lee, Sora and Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 and Qiao, Lan and Josifi, Erlena and Tiao, Joshua R. and Chung, Dai H., E-mail: dai.chung@vanderbilt.edu and Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.},
doi = {10.1016/J.BBRC.2012.06.125},
url = {https://www.osti.gov/biblio/22210165},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 424,
place = {United States},
year = {Fri Aug 03 00:00:00 EDT 2012},
month = {Fri Aug 03 00:00:00 EDT 2012}
}