Expression Patterns and Corepressor Function of Retinoic Acid-induced 2 in Prostate Cancer.

Cell Line, Tumor Co-Repressor Proteins Humans Intercellular Signaling Peptides and Proteins / metabolism Male Neoplastic Cells, Circulating / pathology Prostatic Neoplasms / genetics Receptors, Androgen / genetics Tretinoin / pharmacology
androgen deprivation therapy androgen receptor biochemical recurrence circulating tumor cells metastasis prostate cancer

Journal

Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549

Informations de publication

Date de publication:
03 07 2022
Historique:
received: 06 12 2021
accepted: 06 04 2022
pubmed: 3 6 2022
medline: 8 7 2022
entrez: 2 6 2022
Statut: ppublish

Résumé

Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer. We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n = 199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n = 38) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes. Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1. The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.

Sections du résumé

BACKGROUND
Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer.
METHODS
We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n = 199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n = 38) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes.
RESULTS
Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1.
CONCLUSIONS
The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.

Identifiants

DOI: 10.1093/clinchem/hvac073 PMID: 35652463
pubmed: 35652463
pii: 6598033
doi: 10.1093/clinchem/hvac073
doi:

Substances chimiques

Co-Repressor Proteins 0
Intercellular Signaling Peptides and Proteins 0
RAI2 protein, human 0
Receptors, Androgen 0
Tretinoin 5688UTC01R

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

973-983

Informations de copyright

© American Association for Clinical Chemistry 2022.

Auteurs

Katharina Besler (K)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Aleksandra Węglarz (A)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Laura Keller (L)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Gunhild von Amsberg (G)

Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Natalia Bednarz-Knoll (N)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Laboratory of Translational Oncology, Medical University of Gdańsk, Gdańsk, Poland.
ORCID: 0000-0001-9506-942X

Anne Offermann (A)

Institute of Pathology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Sara Stoupiec (S)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Elke Eltze (E)

Institute of Pathology Saarbruecken-Rastpfuhl, Saarbruecken, Germany.

Axel Semjonow (A)

Department of Urology, Prostate Center University Clinic Münster, Münster, Germany.

Lena Boettcher (L)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Svenja Schneegans (S)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Sven Perner (S)

Institute of Pathology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.

Siegfried Hauch (S)

QIAGEN Gmbh, Hilden, Germany.

Tilman Todenhöfer (T)

Medical School, University of Tübingen, Tübingen, Germany.

Sven Peine (S)

Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Klaus Pantel (K)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Harriet Wikman (H)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Stefan Werner (S)

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mildred-Scheel-Nachwuchszentrum HaTRiCs4, Universitäres Cancer Center Hamburg, Hamburg, Germany.
ORCID: 0000-0002-2451-9371

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines corépressives › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Expression Patterns and Corepressor Function...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Cellules tumorales circulantes › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs aux androgènes › Expression Patterns and Corepressor Function...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Caroténoïdes › Rétinoïdes › Trétinoïne › Expression Patterns and Corepressor Function...