PMID- 36901727
OWN - NLM
STAT- MEDLINE
DCOM- 20230316
LR  - 20230316
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 5
DP  - 2023 Feb 21
TI  - The Novel RXR Agonist MSU-42011 Differentially Regulates Gene Expression in 
      Mammary Tumors of MMTV-Neu Mice.
LID - 10.3390/ijms24054298 [doi]
LID - 4298
AB  - Retinoid X receptor (RXR) agonists, which activate the RXR nuclear receptor, are 
      effective in multiple preclinical cancer models for both treatment and 
      prevention. While RXR is the direct target of these compounds, the downstream 
      changes in gene expression differ between compounds. RNA sequencing was used to 
      elucidate the effects of the novel RXRalpha agonist MSU-42011 on the transcriptome in 
      mammary tumors of HER2+ mouse mammary tumor virus (MMTV)-Neu mice. For 
      comparison, mammary tumors treated with the FDA approved RXR agonist bexarotene 
      were also analyzed. Each treatment differentially regulated cancer-relevant gene 
      categories, including focal adhesion, extracellular matrix, and immune pathways. 
      The most prominent genes altered by RXR agonists positively correlate with 
      survival in breast cancer patients. While MSU-42011 and bexarotene act on many 
      common pathways, these experiments highlight the differences in gene expression 
      between these two RXR agonists. MSU-42011 targets immune regulatory and 
      biosynthetic pathways, while bexarotene acts on several proteoglycan and matrix 
      metalloproteinase pathways. Exploration of these differential effects on gene 
      transcription may lead to an increased understanding of the complex biology 
      behind RXR agonists and how the activities of this diverse class of compounds can 
      be utilized to treat cancer.
FAU - Reich, Lyndsey A
AU  - Reich LA
AUID- ORCID: 0000-0001-9737-5164
AD  - Department of Pharmacology and Toxicology, College of Osteopathic Medicine, East 
      Lansing, MI 48824, USA.
FAU - Leal, Ana S
AU  - Leal AS
AD  - Department of Pharmacology and Toxicology, College of Osteopathic Medicine, East 
      Lansing, MI 48824, USA.
FAU - Ellsworth, Edmund
AU  - Ellsworth E
AD  - Department of Pharmacology and Toxicology, College of Osteopathic Medicine, East 
      Lansing, MI 48824, USA.
AD  - Medicinal Chemistry Facility, Michigan State University, East Lansing, MI 48824, 
      USA.
FAU - Liby, Karen T
AU  - Liby KT
AD  - Department of Pharmacology and Toxicology, College of Osteopathic Medicine, East 
      Lansing, MI 48824, USA.
AD  - Department of Pharmacology and Toxicology, Michigan State University, B430 Life 
      Science Building, 1355 Bogue Street, East Lansing, MI 48824, USA.
LA  - eng
GR  - BCRF-20-096/Breast Cancer Research Foundation/
GR  - TSGTD/MSU Targeted Support Grant for Technology Development/
PT  - Journal Article
DEP - 20230221
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - A61RXM4375 (Bexarotene)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Bexarotene
MH  - Gene Expression
MH  - *Mammary Neoplasms, Animal
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Retinoid X Receptors/agonists/metabolism
MH  - *Tetrahydronaphthalenes/pharmacology
PMC - PMC10001983
OTO - NOTNLM
OT  - RXR agonist
OT  - breast cancer
OT  - transcriptomics
COIS- Patent applications covering the novel compounds described in this work have been 
      applied for on behalf of Michigan State University; Ana S. Leal, Edmund 
      Ellsworth, and Karen T. Liby are named inventors on the patent applications. 
      Lyndsey A. Reich declares no competing interest.
EDAT- 2023/03/12 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/02/21
CRDT- 2023/03/11 01:15
PHST- 2023/01/15 00:00 [received]
PHST- 2023/02/15 00:00 [revised]
PHST- 2023/02/19 00:00 [accepted]
PHST- 2023/03/11 01:15 [entrez]
PHST- 2023/03/12 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/21 00:00 [pmc-release]
AID - ijms24054298 [pii]
AID - ijms-24-04298 [pii]
AID - 10.3390/ijms24054298 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 21;24(5):4298. doi: 10.3390/ijms24054298.