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| Status |
Public on Oct 10, 2014 |
| Title |
Densely Ionizing Radiation Effects on the Microenvironment Promote Aggressive Trp53 Null Mammary Carcinomas |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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
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| Overall design |
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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| Contributor(s) |
Illa-Bochaca I, Ouyang H, Tang J, Sebastiano C, Mao J, Costes SV, Demaria S, Barcellos-Hoff MH |
| Citation(s) |
25304265 |
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| Submission date |
Apr 10, 2014 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Mary Helen Barcellos-Hoff |
| Organization name |
New York University
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| Department |
Radiation
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| Street address |
450 29th street
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| City |
new york |
| State/province |
New York |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (45)
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| GSM1367046 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 1 |
| GSM1367047 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 2 |
| GSM1367048 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 3 |
| GSM1367049 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 4 |
| GSM1367050 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 5 |
| GSM1367051 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 6 |
| GSM1367052 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 7 |
| GSM1367053 |
Trp53-null-mammary-tumor, 80 cGy Si-irradiated host repeat 8 |
| GSM1367054 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 1 |
| GSM1367055 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 2 |
| GSM1367056 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 3 |
| GSM1367057 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 4 |
| GSM1367058 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 5 |
| GSM1367059 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 6 |
| GSM1367060 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 7 |
| GSM1367061 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 8 |
| GSM1367062 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 9 |
| GSM1367063 |
Trp53-null-mammary-tumor, 30 cGy Si-irradiated host repeat 10 |
| GSM1367064 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 1 |
| GSM1367065 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 2 |
| GSM1367066 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 3 |
| GSM1367067 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 4 |
| GSM1367068 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 5 |
| GSM1367069 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 6 |
| GSM1367070 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 7 |
| GSM1367071 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 8 |
| GSM1367072 |
Trp53-null-mammary-tumor, 10 cGy Si-irradiated host repeat 9 |
| GSM1367073 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 1 |
| GSM1367074 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 2 |
| GSM1367075 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 3 |
| GSM1367076 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 4 |
| GSM1367077 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 5 |
| GSM1367078 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 6 |
| GSM1367079 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 7 |
| GSM1367080 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 8 |
| GSM1367081 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 9 |
| GSM1367082 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 10 |
| GSM1367083 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 11 |
| GSM1367084 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 12 |
| GSM1367085 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 13 |
| GSM1367086 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 14 |
| GSM1367087 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 15 |
| GSM1367088 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 16 |
| GSM1367089 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 17 |
| GSM1367090 |
Trp53-null-mammary-tumor, sham-irradiated host repeat 18 |
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| Relations |
| BioProject |
PRJNA244345 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56704_RAW.tar |
189.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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