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“Avogadro” large-scale research facilities

ABSTRACT: In this project, the HepG2 cell line sample was studied using standard shotgun and two-dimensional liquid chromatography approaches to enhance the sensitivity of the MS method.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepg2 Cell

SUBMITTER: Viktoriia Arzumanian

LAB HEAD: Ekaterina Poverennaya

PROVIDER: PXD056076 | Pride | 2024-09-29

REPOSITORIES: Pride

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			Action	DRS
	270722X18_HEP_2D01.raw	Raw
	270722X18_HEP_2D01.t.xml.gz	Xml
	270722X18_HEP_2D01_20220727212842.raw	Raw
	270722X18_HEP_2D01_20220727212842.t.xml.gz	Xml
	270722X18_HEP_2D01_20220727232257.raw	Raw

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Project description:Introduction: Over the past several years, we have been interested in understanding the mechanisms by which hormone-dependent (HD) mammary carcinomas grow in the absence of the stimulatory hormone. We have hypothesized that the stromal compartment plays a pivotal role in the acquisition of the hormone-independent (HI) phenotype by providing stimulatory factors that replace the proliferative effects of the hormone. Methods: We used DNA microarrays to compare the gene expression profiles of tumors from the MPA mouse breast cancer model, one hormone-dependent (C4-HD) and one hormone-independent (C4-HI), using whole tumor samples or laser-captured purified stromal and epithelial cells obtained from the same tumors. The expression of selected genes was validated by immunohistochemistry and immunofluorescence assays. Results: We identified 413 genes that were expressed in tumor stroma but not in epithelial cells. Eighty-five percent of these genes were upregulated, whereas the remaining 15% were downregulated in C4-HI tumors relative to their expression in the C4-HD tumor stroma. Several matrix metallopeptidases, including Mmp13, Mmp3, Mmp10 and Mmp9, were overexpressed in the C4-HI tumor microenvironment. On the other hand, 1100 genes were specifically expressed in the tumor parenchyma. Among them, the 29% were upregulated, whereas the remaining 71% were downregulated, in C4-HI relative to C4-HD tumor epithelium. Steap, Pdgfc, Runx2, Cxcl9 and Sdf2 were among the genes with high expression in the C4-HI tumor parenchyma. Interestingly, we found that Fgf2 was one of the few genes upregulated by MPA in C4-HD tumors, confirming its pivotal role in regulating tumor growth in this model. Conclusions: We demonstrate a gene expression profile that distinguishes epithelial from stromal cells in mammary tumors with different hormone dependence. Our results support the hypothesis that the tumor-associated stroma may contribute to hormone-independent tumor growth. The fact that Fgf2 was one of these few stimulatory genes is worth investigating. reference X sample

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“Avogadro” large-scale research facilities

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