Low-dose radiation-induced senescent stromal fibroblasts render nearby breast cancer cells radioresistant

Kelvin K C Tsai, Jeremy Stuart, Yao Yu Eric Chuang, John B. Little, Zhi Min Yuan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In addition to cell cycle arrest, DNA repair or/and apoptosis, ionizing radiation can also induce premature senescence, which could lead to very different biological consequences depending on the cell type. We show in this report that low-dose radiation-induced senescent stromal fibroblasts stimulate proliferation of cocultured breast carcinoma cells. Such effects of senescent fibroblasts appear to result from their ability to induce the expression in carcinoma cells of mitotic genes and subsequent mitotic division. The elevated proliferation of breast carcinoma cells correlates with resistance to radiation as well as to adriamycin. Of interest is the observation that exposure to lower doses (<20 cGy) augments the ability of senescent fibroblasts to promote the survival of cocultured breast carcinoma cells. The resistance appears to be mediated partially by the Akt pathway, because expression of a dominant negative Akt mutant in breast carcinoma cells results in a partial reversal of the radioresistance. The ability of fibroblasts to modulate the radiosensitivity of nearby carcinoma cells implicates the importance of targeting the stroma during therapy.

Original languageEnglish
Pages (from-to)306-313
Number of pages8
JournalRadiation Research
Volume172
Issue number3
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Fingerprint Dive into the research topics of 'Low-dose radiation-induced senescent stromal fibroblasts render nearby breast cancer cells radioresistant'. Together they form a unique fingerprint.

Cite this