GEO series

Loss of aryl hydrocarbon receptor and long-term, but not short-term treatment with BAY2416964 alters gene expression profiles and reduces proliferation and migration of PyMT mammary cancer cells

GSE272215 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/10/08 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 16 samples: 4 × AHRKO, DMSO, vs 4 × WT, DMSO, vs 4 × LT-BAY, DMSO, vs 4 × WT, BAY 24HR,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cellsFrontiers in oncology · 2024

Summary (written by the submitters)

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that drives pro-survival processes that facilitate tumorigenesis, malignant cell migration, invasion, and metastasis. Much of AHR’s pro-tumorigenic action is due to its activation by the oncometabolite, kynurenine. Because of this AHR antagonists are being actively investigated as new anti-tumor therapy.

Read the full summary ↓

In this study we compared the effects of treatment with the AHR antagonists, BAY2416964 and GNF351, to that of AHR knockout in PyMT murine mammary cancer cells. BAY2146964 and GNF351 effectively inhibited kynurenine-dependent increases in Cyp1a1 and Cyp1b1 mRNA levels. However, single doses of 10 mM BAY2416964, but not 10 mM GNF351, exhibited agonist activity reflected by weak increases Cyp1a1 and Cyp1b1 mRNA levels. CRISPR/Cas9-generated PyMT AhrKO cells exhibited reduced cell proliferation compared with controls, but treatment with 1 mM BAY2416964 for 96 h had no effect on the proliferation of wildtype cells. To examine the differences between AHR knockout and short term BAY2416964 further, we generated long-term BAY2416964 (LT-BAY) by exposing wildtype cells to 1 mM BAY2416964 for at least 6 weeks. Similar to AhrKO cells, LT-BAY cells exhibited reduced cell proliferation and migration compared with wildtype cells; although not to the same extent as that observed with AhrKO cells. RNA sequencing studies identified 714 differentially expressed genes (DEGs) that overlapped between LT-BAY and AhrKO cells, but none after 24 h exposure with 1 mM BAY2416964. Our data reveal BAY2416964 exhibits weak AHR agonist activity in PyMT cells and that long-term pharmacological inhibition of AHR more closely mimicked AHR loss.

Published in

Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

Olafsen NE, Das S, Gorrini C et al. · Frontiers in oncology 2024 · PMID 39450255 · doi:10.3389/fonc.2024.1466658

This dataset

Open GSE272215 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE272215_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1135701 and SRA study SRP519805. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39450255) ↗

Study design

4 × AHRKO, DMSO, vs 4 × WT, DMSO, vs 4 × LT-BAY, DMSO, vs 4 × WT, BAY 24HR,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8395862 AHRKO, DMSO, Rep1 AHRKO, DMSO,
GSM8395863 AHRKO, DMSO, Rep2 AHRKO, DMSO,
GSM8395864 AHRKO, DMSO, Rep3 AHRKO, DMSO,
GSM8395865 AHRKO, DMSO, Rep4 AHRKO, DMSO,
GSM8395866 WT, DMSO, Rep1 WT, DMSO,
GSM8395867 WT, DMSO, Rep2 WT, DMSO,
GSM8395868 WT, DMSO, Rep3 WT, DMSO,
GSM8395869 WT, DMSO, Rep4 WT, DMSO,
GSM8395870 LT-BAY, DMSO, Rep1 LT-BAY, DMSO,
GSM8395871 LT-BAY, DMSO, Rep2 LT-BAY, DMSO,
GSM8395872 LT-BAY, DMSO, Rep3 LT-BAY, DMSO,
GSM8395873 LT-BAY, DMSO, Rep4 LT-BAY, DMSO,
GSM8395874 WT, BAY 24HR, Rep1 WT, BAY 24HR,
GSM8395875 WT, BAY 24HR, Rep2 WT, BAY 24HR,
GSM8395876 WT, BAY 24HR, Rep3 WT, BAY 24HR,
GSM8395877 WT, BAY 24HR, Rep4 WT, BAY 24HR,

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