Densely Ionizing Radiation Effects on the Microenvironment Promote Aggressive Trp53 Null Mammary Carcinomas

Metadata Updated: May 1, 2019

Densely ionizing radiation is a major component of the space radiation environment and has potentially greater carcinogenic effect compared to sparsely ionizing radiation that is prevalent in the terrestrial environment. It is unknown to what extent the irradiated microenvironment contributes to the differential carcinogenic potential of densely ionizing radiation. To address this gap 10-week old BALB/c mice were irradiated with 100 cGy sparsely ionizing g-radiation or 10 30 or 80 cGy of densely ionizing 350 MeV/amu Si particles and transplanted 3 days later with syngeneic Trp53 null mammary fragments. Tumor appearance was monitored for 600 days. Tumors arising in Si-particle irradiated mice had a shorter median time to appearance grew faster and were more likely to metastasize. Most tumors arising in sham-irradiated mice were ER-positive pseudo-glandular and contained both basal keratin 14 and luminal keratin 8/18 cells (designated K14/18) while most tumors arising in irradiated hosts were K8/18 positive (designated K18) and ER negative. Comparison of K18 vs K14/18 tumor expression profiles showed that genes increased in K18 tumors were associated with ERBB2 and KRAS while decreased genes overlapped with those down regulated in metastasis and by loss of E-cadherin. Consistent with this K18 tumors grew faster than K14/18 tumors and more mice with K18 tumors developed lung metastases compared to mice with K14/18 tumors. However K18 tumors arising in Si-particle irradiated mice grew even faster and were more metastatic compared to control mice. A K18 Si-irradiated host profile was enriched in genes involved in mammary stem cells stroma and Notch signaling. Thus systemic responses to densely ionizing radiation enriches for a ER-negative K18-positive tumor whose biology is more aggressive compared to similar tumors arising in non-irradiated hosts. Key Words: ionizing radiation; breast cancer; heavy ion radiation;initiation; promotion 3 different dose of Si were used. Total RNA was extracted from mammary tumors derived from transplantations of non-irradiated p53null mammary fragments into irradiated hosts. We analyzed a total of 45 Trp53-null tumors: 18 from sham-irradiated hosts 9 from 10 cGy Si-irradiated hosts 10 from 30 cGy Si-irradiated hosts and 8 from irradiated hosts.

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Public: This dataset is intended for public access and use. License: U.S. Government Work

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Metadata Created Date August 1, 2018
Metadata Updated Date May 1, 2019
Data Update Frequency irregular

Metadata Source

Harvested from NASA Data.json

Additional Metadata

Resource Type Dataset
Metadata Created Date August 1, 2018
Metadata Updated Date May 1, 2019
Publisher National Aeronautics and Space Administration
Unique Identifier nasa_genelab_GLDS-74
GeneLab Outreach
Maintainer Email
Public Access Level public
Data Update Frequency irregular
Bureau Code 026:00
Metadata Context
Metadata Catalog ID
Schema Version
Catalog Describedby
Datagov Dedupe Retained 20190501230127
Harvest Object Id b693ae56-8f17-47b8-ba06-c8b1ab498917
Harvest Source Id 39e4ad2a-47ca-4507-8258-852babd0fd99
Harvest Source Title NASA Data.json
Data First Published 2018-06-26
Homepage URL
Data Last Modified 2018-07-19
Program Code 026:005
Source Datajson Identifier True
Source Hash e9a4f0d01a24b2c6cbbf9891f2ecad2caa94de93
Source Schema Version 1.1
Category Earth Science

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