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Title: An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

Journal Article · · Oncotarget
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  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
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The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent gene cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1407216
Journal Information:
Oncotarget, Vol. 5, Issue 12; ISSN 1949-2553
Publisher:
Impact JournalsCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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Cited By (9)

Transcriptional repression of IFNβ1 by ATF2 confers melanoma resistance to therapy journal March 2015
A generic cycling hypoxia-derived prognostic gene signature: application to breast cancer profiling journal July 2014
Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response journal March 2019
Conservation of immune gene signatures in solid tumors and prognostic implications journal November 2016
Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis journal March 2019
Two-Tier Mapper, an unbiased topology-based clustering method for enhanced global gene expression analysis journal February 2019
Type I interferons in anticancer immunity journal June 2015
Genetic Background Modulates lncRNA-Coordinated Tissue Response to Low Dose Ionizing Radiation journal January 2015
Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of 56 Fe particles: Individual Variation in Dose Response for Learning journal May 2016

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Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
estrous cycle
mammary glad
RNA-sequencing
Type-1 interferon
low-dose radiation (LDIR)
immunity
breast cancer
genetic susceptibility