Simulated galactic cosmic radiation (GCR)-induced expression of Spp1 coincide with mammary ductal cell proliferation and preneoplastic changes in Apc mouse

Kumar, K. Ravi; Moon, Bo‐Hyun; Datta, Kamal; Fornace, Albert J.; Suman, Shubhankar

doi:10.1016/j.lssr.2022.09.006

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Female astronauts face in-space galactic cosmic radiation (GCR) and have a greater risk for breast cancer development [ 204 ]. Simulated GCR-induced expression of Spp1 coincide with mammary ductal cell proliferation and preneoplastic changes in an Apc Min/+ mouse model [ 204 ].…”

Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks

Wadhwa,

Moreno-Villanueva,

Crucian

et al. 2024

Immun Ageing

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Spaceflight poses a myriad of environmental stressors to astronauts´ physiology including microgravity and radiation. The individual impacts of microgravity and radiation on the immune system have been extensively investigated, though a comprehensive review on their combined effects on immune system outcomes is missing. Therefore, this review aims at understanding the synergistic, additive, and antagonistic interactions between microgravity and radiation and their impact on immune function as observed during spaceflight-analog studies such as rodent hindlimb unloading and cell culture rotating wall vessel models. These mimic some, but not all, of the physiological changes observed in astronauts during spaceflight and provide valuable information that should be considered when planning future missions. We provide guidelines for the design of further spaceflight-analog studies, incorporating influential factors such as age and sex for rodent models and standardizing the longitudinal evaluation of specific immunological alterations for both rodent and cellular models of spaceflight exposure.

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Simulated Galactic Cosmic Radiation Exposure-Induced Mammary Tumorigenesis in ApcMin/+ Mice Coincides with Activation of ERα-ERRα-SPP1 Signaling Axis

Kumar,

Angdisen,

et al. 2024

Cancers

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Background: Exposure to galactic cosmic radiation (GCR) is a breast cancer risk factor for female astronauts on deep-space missions. However, the specific signaling mechanisms driving GCR-induced breast cancer have not yet been determined. Methods: This study aimed to investigate the role of the estrogen-induced ERα-ERRα-SPP1 signaling axis in relation to mammary tumorigenesis in female ApcMin/+ mice exposed to simulated GCR (GCRsim) at 100–110 days post-exposure. Results: In GCRsim-exposed mice, we observed marked elevations in serum estradiol, increased ductal overgrowth, ERα activation, and upregulation of ERα target genes with pro-tumorigenic functions in mammary tissues that was coupled with a higher mammary tumorigenesis, relative to control. Additionally, the ERα target gene Esrra, which encodes ERRα, was also upregulated along with its oncogenic target gene Spp1, indicating the activation of the ERα-ERRα-SPP1 axis in mouse mammary tissues after GCRsim exposure. Using a human tissue microarray and human breast cancer gene expression analysis, we also highlighted the conserved nature of the ERα-ERRα-SPP1 signaling in human breast cancer development. Conclusions: We identified the ERα-ERRα-SPP1 signaling axis as a potential key mediator in GCR-induced breast cancer with conserved activation in human breast cancer. These findings suggest that targeting this pathway could serve as a potential target for therapeutic intervention to safeguard female astronauts during and after a prolonged outer space mission.

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Simulated galactic cosmic radiation (GCR)-induced expression of Spp1 coincide with mammary ductal cell proliferation and preneoplastic changes in Apc mouse

Cited by 4 publications

References 57 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks

Simulated Galactic Cosmic Radiation Exposure-Induced Mammary Tumorigenesis in ApcMin/+ Mice Coincides with Activation of ERα-ERRα-SPP1 Signaling Axis

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