TY - JOUR
T1 - mRNA Expression profiles for prostate cancer following fractionated irradiation are influenced by p53 status
AU - Simone, Charles B.
AU - John-Aryankalayil, Molykutty
AU - Palayoor, Sanjeewani T.
AU - Makinde, Adeola Y.
AU - Cerna, David
AU - Falduto, Michael T.
AU - Magnuson, Scott R.
AU - Coleman, C. Norman
N1 - Funding Information:
Address all correspondence to: Charles B. Simone, II, MD, Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, TRC 2 West, Philadelphia, PA 19104. E-mail: csimone@alumni.upenn.edu 1This work was supported by the intramural research program of the National Institutes of Health (NIH), National Cancer Institute, and Center for Cancer Research. All experimentations were performed at the NIH. Conflict of interest: none. 2This article refers to supplementary materials, which are designated by Tables W1 to W4 and are available online at www.transonc.com. Received 25 February 2013; Revised 20 July 2013; Accepted 24 July 2013 Copyright © 2013 Neoplasia Press, Inc. OpenaccessunderCCBY-NC-NDlicense. 1944-7124/13 DOI 10.1593/tlo.13241
PY - 2013/10
Y1 - 2013/10
N2 - We assessed changes in cell lines of varying p53 status after various fractionation regimens to determine if p53 influences gene expression and if multifractionated (MF) irradiation can induce molecular pathway changes. LNCaP (p53 wild-type), PC3 (p53 null), and DU145 (p53 mutant) prostate carcinoma cells received 5 and 10 Gy as single-dose (SD) or MF (0.5 Gy × 10, 1 Gy × 10, and 2 Gy × 5) irradiation to simulate hypofractionated and conventionally fractionated prostate radiotherapies, respectively. mRNA analysis revealed 978 LNCaP genes differentially expressed (greater than two-fold change, P <.05) after irradiation. Most were altered with SD (69%) and downregulated (75%). Fewer PC3 (343) and DU145 (116) genes were induced, with most upregulated (87%, 89%) and altered with MF irradiation. Gene ontology revealed immune response and interferon genes most prominently expressed after irradiation in PC3 and DU145. Cell cycle regulatory (P = 9.23 × 10-73, 14.2% of altered genes, nearly universally downregulated) and DNA replication/repair (P = 6.86 × 10-30) genes were most prominent in LNCaP. Stress response and proliferation genes were altered in all cell lines. p53-activated genes were only induced in LNCaP. Differences in gene expression exist between cell lines and after varying irradiation regimens that are p53 dependent. As the duration of changes is ≥24 hours, it may be possible to use radiation-inducible targeted therapy to enhance the efficacy of molecular targeted agents.
AB - We assessed changes in cell lines of varying p53 status after various fractionation regimens to determine if p53 influences gene expression and if multifractionated (MF) irradiation can induce molecular pathway changes. LNCaP (p53 wild-type), PC3 (p53 null), and DU145 (p53 mutant) prostate carcinoma cells received 5 and 10 Gy as single-dose (SD) or MF (0.5 Gy × 10, 1 Gy × 10, and 2 Gy × 5) irradiation to simulate hypofractionated and conventionally fractionated prostate radiotherapies, respectively. mRNA analysis revealed 978 LNCaP genes differentially expressed (greater than two-fold change, P <.05) after irradiation. Most were altered with SD (69%) and downregulated (75%). Fewer PC3 (343) and DU145 (116) genes were induced, with most upregulated (87%, 89%) and altered with MF irradiation. Gene ontology revealed immune response and interferon genes most prominently expressed after irradiation in PC3 and DU145. Cell cycle regulatory (P = 9.23 × 10-73, 14.2% of altered genes, nearly universally downregulated) and DNA replication/repair (P = 6.86 × 10-30) genes were most prominent in LNCaP. Stress response and proliferation genes were altered in all cell lines. p53-activated genes were only induced in LNCaP. Differences in gene expression exist between cell lines and after varying irradiation regimens that are p53 dependent. As the duration of changes is ≥24 hours, it may be possible to use radiation-inducible targeted therapy to enhance the efficacy of molecular targeted agents.
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U2 - 10.1593/tlo.13241
DO - 10.1593/tlo.13241
M3 - Article
AN - SCOPUS:84885810629
VL - 6
SP - 573
EP - 585
JO - Translational Oncology
JF - Translational Oncology
SN - 1936-5233
IS - 5
ER -