Altered RBP1 Gene Expression Impacts Epithelial Cell Retinoic Acid, Proliferation, and Microenvironment.

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Vitamin A is crucial for biological functions, with all-trans retinoic acid (atRA) being its active metabolite.
• Retinol-binding protein 1 (RBP1) facilitates atRA biosynthesis and its expression is often reduced in prevalent cancers like breast cancer.

Purpose of the Study:

• To investigate the relationship between RBP1 expression and atRA biosynthesis in mammary epithelial cells and human mammary tissue.
• To explore the impact of RBP1 and atRA on the tumor microenvironment.
• To assess therapeutic strategies for restoring RBP1 expression and endogenous atRA production.

Main Methods:

• Utilized human mammary ductal carcinoma samples and epithelial cell lines.
• Quantified RBP1 expression via qPCR and atRA levels via liquid chromatography-tandem mass spectrometry.
• Assessed functional effects using qPCR for atRA targets, Ki-67 staining for proliferation, and picrosirius red staining for collagen deposition.

Main Results:

• RBP1 and atRA levels were found to be reduced in mammary tumor tissues and tumorigenic cell lines.
• RBP1 knockdown or overexpression demonstrated a direct correlation with atRA levels.
• Therapeutic interventions (AM580, Decitabine) successfully increased RBP1 expression and atRA levels, impacting proliferation and collagen deposition.

Conclusions:

• A direct relationship exists between RBP1 expression and atRA levels, which can be therapeutically restored.
• Conditions in the tumor microenvironment, such as hypoxia, can decrease RBP1 and atRA.
• Diseases with reduced RBP1 may benefit from therapies that restore RBP1 expression and endogenous atRA production.