TY - JOUR
T1 - Rarβ expression in keratinocytes from potentially malignant oral lesions
T2 - The functional consequences of re-expression by de-methylating agents
AU - Radhakrishnan, Raghu
AU - Crane, Hannah L.
AU - Daigneault, Marc
AU - Padam, Kanaka Sai Ram
AU - Hunter, Keith D.
N1 - Funding Information:
This research was funded by the European Commission FP7 Marie Curie Incoming Fel-lowship, grant number PIIF-GA-2012-327300.
Funding Information:
Funding: This research was funded by the European Commission FP7 Marie Curie Incoming Fellowship, grant number PIIF-GA-2012-327300.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/2
Y1 - 2021/8/2
N2 - Loss of RARβ2 expression by promoter methylation is an early event in oral carcinogene-sis. Understanding the mechanisms and consequences of RARβ loss may aid in understanding the disappointing results of retinoid chemoprevention trials. This study aimed to describe the effects of all-trans retinoic acid (ATRA) and the de-methylating agent 5-Aza-2′ deoxycytidine (5-AZA-CdR) on a panel of immortal potentially malignant oral lesion (PMOL) cell cultures. RARβ expression was assessed in PMOL tissues by immunohistochemistry. Cells were treated with ATRA ± 5-AZA-CdR, and the effects on the cell cycle and senescence were assessed. In PMOL tissues, RARβ expression was variable, but lower in biopsies which gave rise to immortal cell cultures. Treatment of iPMOL cells with ATRA resulted in little change in RARβ expression, but the addition of 5-AZA-CdR resulted in significant increases. The effects on the cell cycle and senescence were variable and may be related to 5-AZA-CdR, as this has wider effects on the cell cycle. Overall, the response of iPMOL cells to ATRA and 5-AZA-CdR treatment was variable and is dependent on several factors, including RARβ-promoter methylation. These findings may help to explain the lack of consistent effect of retinoids in PMOLs seen in chemoprevention trials.
AB - Loss of RARβ2 expression by promoter methylation is an early event in oral carcinogene-sis. Understanding the mechanisms and consequences of RARβ loss may aid in understanding the disappointing results of retinoid chemoprevention trials. This study aimed to describe the effects of all-trans retinoic acid (ATRA) and the de-methylating agent 5-Aza-2′ deoxycytidine (5-AZA-CdR) on a panel of immortal potentially malignant oral lesion (PMOL) cell cultures. RARβ expression was assessed in PMOL tissues by immunohistochemistry. Cells were treated with ATRA ± 5-AZA-CdR, and the effects on the cell cycle and senescence were assessed. In PMOL tissues, RARβ expression was variable, but lower in biopsies which gave rise to immortal cell cultures. Treatment of iPMOL cells with ATRA resulted in little change in RARβ expression, but the addition of 5-AZA-CdR resulted in significant increases. The effects on the cell cycle and senescence were variable and may be related to 5-AZA-CdR, as this has wider effects on the cell cycle. Overall, the response of iPMOL cells to ATRA and 5-AZA-CdR treatment was variable and is dependent on several factors, including RARβ-promoter methylation. These findings may help to explain the lack of consistent effect of retinoids in PMOLs seen in chemoprevention trials.
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U2 - 10.3390/cancers13164064
DO - 10.3390/cancers13164064
M3 - Article
AN - SCOPUS:85112320760
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 16
M1 - 4064
ER -
