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Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

Publication ,  Journal Article
Lee, C-T; Zhou, Y; Roy-Choudhury, K; Siamakpour-Reihani, S; Young, K; Hoang, P; Kirkpatrick, JP; Chi, J-T; Dewhirst, MW; Horton, JK
Published in: Radiat Res
August 2017

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2+) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

Duke Scholars

Published In

Radiat Res

DOI

EISSN

1938-5404

Publication Date

August 2017

Volume

188

Issue

2

Start / End Page

169 / 180

Location

United States

Related Subject Headings

  • fas Receptor
  • Treatment Outcome
  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Silencing
  • Gene Expression Regulation, Neoplastic
  • Female
  • Fas Ligand Protein
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lee, C.-T., Zhou, Y., Roy-Choudhury, K., Siamakpour-Reihani, S., Young, K., Hoang, P., … Horton, J. K. (2017). Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer. Radiat Res, 188(2), 169–180. https://doi.org/10.1667/RR14664.1
Lee, Chen-Ting, Yingchun Zhou, Kingshuk Roy-Choudhury, Sharareh Siamakpour-Reihani, Kenneth Young, Peter Hoang, John P. Kirkpatrick, Jen-Tsan Chi, Mark W. Dewhirst, and Janet K. Horton. “Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.Radiat Res 188, no. 2 (August 2017): 169–80. https://doi.org/10.1667/RR14664.1.
Lee C-T, Zhou Y, Roy-Choudhury K, Siamakpour-Reihani S, Young K, Hoang P, et al. Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer. Radiat Res. 2017 Aug;188(2):169–80.
Lee, Chen-Ting, et al. “Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.Radiat Res, vol. 188, no. 2, Aug. 2017, pp. 169–80. Pubmed, doi:10.1667/RR14664.1.
Lee C-T, Zhou Y, Roy-Choudhury K, Siamakpour-Reihani S, Young K, Hoang P, Kirkpatrick JP, Chi J-T, Dewhirst MW, Horton JK. Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer. Radiat Res. 2017 Aug;188(2):169–180.

Published In

Radiat Res

DOI

EISSN

1938-5404

Publication Date

August 2017

Volume

188

Issue

2

Start / End Page

169 / 180

Location

United States

Related Subject Headings

  • fas Receptor
  • Treatment Outcome
  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Silencing
  • Gene Expression Regulation, Neoplastic
  • Female
  • Fas Ligand Protein