Dataset Information

Tandem Mass Tag-Based Quantitative Proteomics of Extracellular Vesicles Isolated from Mammary Fibroblasts Treated with γ-radiation

ABSTRACT: Small extracellular vesicles (EVs) were isolated from a model of normal breast fibroblasts— immortalized cells derived from healthy reduction mammoplasty tissue—treated with γ-radiation to study the effects of radiation therapy on intercellular communication within the breast stroma. EVs were isolated using the gold-standard differential speed centrifugation protocol. Proteins were extracted and analyzed using a TMT-based quantitative proteomics approach.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast Of Breast, Breast

SUBMITTER: Kristie Lindsey Rose

LAB HEAD: Kristie Lindsey Rose

PROVIDER: PXD066811 | Pride | 2026-06-01

REPOSITORIES: Pride

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			Action	DRS
	checksum.txt	Txt
	pEX1_pp_6349_20240125_TMT4plex_BRP_F1_0pt3uL_1.raw	Raw
	pEX1_pp_6349_20240125_TMT4plex_BRP_F2_0pt4uL_2.raw	Raw
	pEX1_pp_6349_20240125_TMT4plex_BRP_F3_0pt3uL_3.raw	Raw
	pEX1_pp_6349_20240125_TMT4plex_BRP_F4_0pt3uL_4.raw	Raw

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Publications

Mammary Fibroblasts Secrete Damage Associated Molecular Patterns Through Extracellular Vesicles in Response to Ionizing Radiation.

Berumen Sánchez Greg G Patel Purvi P Gomez-Crase Preston P Kim Chloe C Corn Kevin C KC Rose Kristie L KL Rafat Marjan M

Journal of extracellular biology 20260515

Ionizing radiation (IR) is an integral component of cancer therapy. Cellular exposure to IR typically leads to major biological consequences including cell death and senescence. Furthermore, tissue injury is known to involve the release of damage-associated molecular patterns (DAMPs) into the extracellular space, which trigger inflammation and wound healing. However, DAMP release in the context of radiation injury remains to be fully characterized. Evidence suggests that extracellular vesicle (E ...[more]

PMID: 42145898

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Project description:This is a genome-wide approach to identifying genes persistently induced in the mouse mammary gland by acute whole body low dose ionizing radiation (10cGy), 1 and 4 weeks after exposure. Gene expression that is modified under these parameters were compared between Tgfb1 wild type and heterozygote littermates in order to determine which genes induced or repressed by radiation were mediated via Tgfb1 status. Differential gene expression was analyzed in Tgfb1 heterozygote and wild type littermate 4th mammary glands, after whole body exposure to an acute dose of 10cGy ionizing radiation. Estrus cycle was normalized in all mice two days prior to irradiation by injection with an estrogen and progesterone mixture. It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor beta 1 (TGFbeta) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. Gene expression profiling shown herein demonstrates that low dose radiation (10 cGy) elicits persistent changes in Tgfb1 wild type and heterozygote murine mammary gland that are highly modulated by TGFbeta. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma, as well as those tumors negative for smooth muscle actin in wild type but not Tgfb1 heterozygote mice. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGFbeta activity is a key mechanism of tumor promotion. Keywords: Differential gene expression after low dose irradiation Two genotypes: TGBbeta1 heterozygote and wildtype mouse mammary glands. Two time points post-10cGy-irradiation per genotype (1 week, 4 weeks); control time point was 1 week post-sham-irradiation. Two or three replicates per time point.