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Gene expression profiling of 4T1 cells isolated from primary tumour or from spontaneous metastases sites

ABSTRACT: Gene expression profiling of 4T1 cells isolated from primary tumour or from spontaneous metastases sites

PROVIDER: PRJNA432749 | ENA |

REPOSITORIES: ENA

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Gene expression profiling of 4T1 cells isolated from primary tumour or from spontaneous metastases sites

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Expression data from 4T1 subclones derived from mammary fat pad tumors (MFP), axillary lymph node tumors (AxLN), and axillary lymph node-derived lung metastases (AxLN-LuM)

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Project description:Metastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indicated by bioluminescence imaging (BLI), and matched subcutaneous primary tumors. Corresponding histology proved the human origin of metastatic lesions. Ovarian metastases were commonly larger than liver metastases indicating differential outgrowth capacities. Among ~1,700 proteins identified at each of the three sites, 89 proteins were differentially regulated in ovarian metastases while 290 proteins were regulated in liver metastases. There was an overlap of 26 and 10 proteins up- and down-regulated at both metastatic sites, respectively, most of which were so far not related to metastasis such as LYPLA2, ACTL8, EIF4B, LGALS7, GFAP, and ELAVL4. Moreover, we established in vitro sublines from primary tumor and metastases and demonstrate differences in cellular protrusions, migratory/invasive potential and glycosylation. Summarized, this work identified several novel putative drivers of metastasis formation that are tempting candidates for future functional studies.

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Project description:4T1 mouse tumour single cell dataset for virtual reality exploration

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Project description:DNMT3B enrichment in lung metastases of 4T1 mouse mammry tumor model

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E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis

Project description:The specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of βcatenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs. Gene expression was compared between normal mouse skin, skin from transgenic RbF/F;K14creERTM; E2F1-/- , E2F1-/-, and RbF/F;K14creERTM; E2F1-/- mouse, and carcinomas arising in the skin of RbF/F;K14creERTM; E2F1-/- mouse. All mice were treated with tamoxifen.

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