Fractionated and acute irradiation induced signaling in a murine tumor

Anirban Mitra, Malini Krishna

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The effect of fractionated doses of Co60 γ-irradiation (2 Gy per fraction over 5 days), as is delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in Swiss mice. The aspects that were studied included the three major mitogen-activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and stress-activated protein (SAP) kinase, which are known to be involved in determining the cell fate following exposure to ionizing radiation. The response of dual specificity phosphatase PAC1 which is involved in the dephosphorylation of MAP kinases was also looked at. There were significant differences in the response to different dose regimens for all the factors studied. Fractionated irradiation elicited an adaptive response with a sustained activation over 7 days of prosurvival p44 MAP kinase which was balanced by the increased activation of proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated p38 MAP kinase showed a decrease at most time points. PAC1 was induced following fractionated irradiation and may be acting as a feed back regulator of p44 MAP kinase. The activation of SAP kinase after fractionated irradiation may be a stress response, whereas, constitutively activated p44 MAP kinase may play an important role in the induction of radioresistance during fractionated radiotherapy of cancer and may serve as a promising target for specific inhibitors to enhance the efficacy of radiotherapy.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalJournal of Cellular Biochemistry
Volume101
Issue number3
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinases
Tumors
Irradiation
Radiotherapy
p38 Mitogen-Activated Protein Kinases
Heat-Shock Proteins
Protein Kinases
Chemical activation
Neoplasms
Dosimetry
Dual-Specificity Phosphatases
Fibrosarcoma
Ionizing radiation
Ionizing Radiation
Feedback

Keywords

  • Fractionated irradiation
  • p38 MAP kinase
  • p44 MAP kinase
  • p54 SAP kinase and PAC1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fractionated and acute irradiation induced signaling in a murine tumor. / Mitra, Anirban; Krishna, Malini.

In: Journal of Cellular Biochemistry, Vol. 101, No. 3, 01.06.2007, p. 745-752.

Research output: Contribution to journalArticle

@article{3ed37bcf93c34d8f9b441a0670138a2a,
title = "Fractionated and acute irradiation induced signaling in a murine tumor",
abstract = "The effect of fractionated doses of Co60 γ-irradiation (2 Gy per fraction over 5 days), as is delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in Swiss mice. The aspects that were studied included the three major mitogen-activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and stress-activated protein (SAP) kinase, which are known to be involved in determining the cell fate following exposure to ionizing radiation. The response of dual specificity phosphatase PAC1 which is involved in the dephosphorylation of MAP kinases was also looked at. There were significant differences in the response to different dose regimens for all the factors studied. Fractionated irradiation elicited an adaptive response with a sustained activation over 7 days of prosurvival p44 MAP kinase which was balanced by the increased activation of proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated p38 MAP kinase showed a decrease at most time points. PAC1 was induced following fractionated irradiation and may be acting as a feed back regulator of p44 MAP kinase. The activation of SAP kinase after fractionated irradiation may be a stress response, whereas, constitutively activated p44 MAP kinase may play an important role in the induction of radioresistance during fractionated radiotherapy of cancer and may serve as a promising target for specific inhibitors to enhance the efficacy of radiotherapy.",
keywords = "Fractionated irradiation, p38 MAP kinase, p44 MAP kinase, p54 SAP kinase and PAC1",
author = "Anirban Mitra and Malini Krishna",
year = "2007",
month = "6",
day = "1",
doi = "10.1002/jcb.21234",
language = "English (US)",
volume = "101",
pages = "745--752",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Fractionated and acute irradiation induced signaling in a murine tumor

AU - Mitra, Anirban

AU - Krishna, Malini

PY - 2007/6/1

Y1 - 2007/6/1

N2 - The effect of fractionated doses of Co60 γ-irradiation (2 Gy per fraction over 5 days), as is delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in Swiss mice. The aspects that were studied included the three major mitogen-activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and stress-activated protein (SAP) kinase, which are known to be involved in determining the cell fate following exposure to ionizing radiation. The response of dual specificity phosphatase PAC1 which is involved in the dephosphorylation of MAP kinases was also looked at. There were significant differences in the response to different dose regimens for all the factors studied. Fractionated irradiation elicited an adaptive response with a sustained activation over 7 days of prosurvival p44 MAP kinase which was balanced by the increased activation of proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated p38 MAP kinase showed a decrease at most time points. PAC1 was induced following fractionated irradiation and may be acting as a feed back regulator of p44 MAP kinase. The activation of SAP kinase after fractionated irradiation may be a stress response, whereas, constitutively activated p44 MAP kinase may play an important role in the induction of radioresistance during fractionated radiotherapy of cancer and may serve as a promising target for specific inhibitors to enhance the efficacy of radiotherapy.

AB - The effect of fractionated doses of Co60 γ-irradiation (2 Gy per fraction over 5 days), as is delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in Swiss mice. The aspects that were studied included the three major mitogen-activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and stress-activated protein (SAP) kinase, which are known to be involved in determining the cell fate following exposure to ionizing radiation. The response of dual specificity phosphatase PAC1 which is involved in the dephosphorylation of MAP kinases was also looked at. There were significant differences in the response to different dose regimens for all the factors studied. Fractionated irradiation elicited an adaptive response with a sustained activation over 7 days of prosurvival p44 MAP kinase which was balanced by the increased activation of proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated p38 MAP kinase showed a decrease at most time points. PAC1 was induced following fractionated irradiation and may be acting as a feed back regulator of p44 MAP kinase. The activation of SAP kinase after fractionated irradiation may be a stress response, whereas, constitutively activated p44 MAP kinase may play an important role in the induction of radioresistance during fractionated radiotherapy of cancer and may serve as a promising target for specific inhibitors to enhance the efficacy of radiotherapy.

KW - Fractionated irradiation

KW - p38 MAP kinase

KW - p44 MAP kinase

KW - p54 SAP kinase and PAC1

UR - http://www.scopus.com/inward/record.url?scp=34247889977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247889977&partnerID=8YFLogxK

U2 - 10.1002/jcb.21234

DO - 10.1002/jcb.21234

M3 - Article

VL - 101

SP - 745

EP - 752

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 3

ER -