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Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model

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Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model. / Coates, Philip J. (Lead / Corresponding author); Appleyard, M. Virginia C. L.; Murray, Karen; Ackland, Caroline; Gardner, June; Brown, Douglas C.; Adamson, Dougal J. A.; Jordan, Lee B.; Purdie, Colin A.; Munro, Alastair J.; Wright, Eric G.; Dewar, John A.; Thompson, Alastair M.

In: Cancer Research, Vol. 70, No. 23, 01.12.2010, p. 9808-9815.

Research output: Contribution to journalArticle

Harvard

Coates, PJ, Appleyard, MVCL, Murray, K, Ackland, C, Gardner, J, Brown, DC, Adamson, DJA, Jordan, LB, Purdie, CA, Munro, AJ, Wright, EG, Dewar, JA & Thompson, AM 2010, 'Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model' Cancer Research, vol 70, no. 23, pp. 9808-9815.

APA

Coates, P. J., Appleyard, M. V. C. L., Murray, K., Ackland, C., Gardner, J., Brown, D. C., Adamson, D. J. A., Jordan, L. B., Purdie, C. A., Munro, A. J., Wright, E. G., Dewar, J. A., & Thompson, A. M. (2010). Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model. Cancer Research, 70(23), 9808-9815doi: 10.1158/0008-5472.CAN-10-1118

Vancouver

Coates PJ, Appleyard MVCL, Murray K, Ackland C, Gardner J, Brown DC et al. Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model. Cancer Research. 2010 Dec 1;70(23):9808-9815.

Author

Coates, Philip J. (Lead / Corresponding author); Appleyard, M. Virginia C. L.; Murray, Karen; Ackland, Caroline; Gardner, June; Brown, Douglas C.; Adamson, Dougal J. A.; Jordan, Lee B.; Purdie, Colin A.; Munro, Alastair J.; Wright, Eric G.; Dewar, John A.; Thompson, Alastair M. / Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model.

In: Cancer Research, Vol. 70, No. 23, 01.12.2010, p. 9808-9815.

Research output: Contribution to journalArticle

Bibtex - Download

@article{ff43685355734f6d8d2fdb9f54dd8ee6,
title = "Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model",
author = "Coates, {Philip J.} and Appleyard, {M. Virginia C. L.} and Karen Murray and Caroline Ackland and June Gardner and Brown, {Douglas C.} and Adamson, {Dougal J. A.} and Jordan, {Lee B.} and Purdie, {Colin A.} and Munro, {Alastair J.} and Wright, {Eric G.} and Dewar, {John A.} and Thompson, {Alastair M.}",
year = "2010",
volume = "70",
number = "23",
pages = "9808--9815",
journal = "Cancer Research",
issn = "0008-5472",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Differential contextual responses of normal human breast epithelium to Ionizing radiation in a mouse xenograft model

A1 - Coates,Philip J.

A1 - Appleyard,M. Virginia C. L.

A1 - Murray,Karen

A1 - Ackland,Caroline

A1 - Gardner,June

A1 - Brown,Douglas C.

A1 - Adamson,Dougal J. A.

A1 - Jordan,Lee B.

A1 - Purdie,Colin A.

A1 - Munro,Alastair J.

A1 - Wright,Eric G.

A1 - Dewar,John A.

A1 - Thompson,Alastair M.

AU - Coates,Philip J.

AU - Appleyard,M. Virginia C. L.

AU - Murray,Karen

AU - Ackland,Caroline

AU - Gardner,June

AU - Brown,Douglas C.

AU - Adamson,Dougal J. A.

AU - Jordan,Lee B.

AU - Purdie,Colin A.

AU - Munro,Alastair J.

AU - Wright,Eric G.

AU - Dewar,John A.

AU - Thompson,Alastair M.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - <p>Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed Delta Np63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of gamma-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems. Cancer Res; 70( 23); 9808-15. (C)2010 AACR.</p>

AB - <p>Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed Delta Np63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of gamma-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems. Cancer Res; 70( 23); 9808-15. (C)2010 AACR.</p>

KW - TARGETED INTRAOPERATIVE RADIOTHERAPY

KW - MAMMARY-GLAND DEVELOPMENT

KW - NORMAL-TISSUE-REACTIONS

KW - ATHYMIC NUDE-MICE

KW - IN-VIVO

KW - CANCER RISK

KW - ATAXIA-TELANGIECTASIA

KW - GAMMA-IRRADIATION

KW - P53 EXPRESSION

KW - INDUCTION

U2 - 10.1158/0008-5472.CAN-10-1118

DO - 10.1158/0008-5472.CAN-10-1118

M1 - Article

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 23

VL - 70

SP - 9808

EP - 9815

ER -

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