Cell Line, Tumor
Cyclin D1
/ metabolism
Gene Knockdown Techniques
Humans
Leukemia, Myeloid
/ genetics
Phosphorylation
Proto-Oncogene Proteins
/ metabolism
RNA, Small Interfering
Receptor Protein-Tyrosine Kinases
/ genetics
STAT3 Transcription Factor
/ metabolism
c-Mer Tyrosine Kinase
/ metabolism
Axl Receptor Tyrosine Kinase
TAM family
TYRO3
leukaemia
small interfering RNA
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
08
02
2022
revised:
27
02
2022
accepted:
28
02
2022
entrez:
29
3
2022
pubmed:
30
3
2022
medline:
5
4
2022
Statut:
ppublish
Résumé
TYRO3 is a member of the TAM family (TYRO3, AXL, and MERTK) of receptor tyrosine kinases. While the roles of activated AXL and MERTK in the growth of leukaemia cells have been reported, the effect of TYRO3 has not been determined. Therefore, we examined the effects of TYRO3 knockdown on the growth of leukaemia cell lines. Three human leukaemia cell lines (AA derived from pure erythroid leukaemia, OCI/AML2, and K562), which express TYRO3 protein were used in this study. To induce TYRO3 knockdown, small interfering RNA (siRNA) against TYRO3 was transfected using an electroporation system. Cell growth was assessed by a colorimetric assay. The expression levels and activation of various signalling proteins were examined by immunoblotting. Changes in comprehensive gene expression after TYRO3 knockdown were examined by microarray analysis. TYRO3 knockdown suppressed cell growth in the leukaemia cell lines tested. Additionally, the knockdown suppressed phosphorylation of signal transducer and activator of transcription-3 in AA cells, and extracellular signal-regulated kinase (ERK) 1/2 in AA and OCI/AML2 cells; both are downstream molecules of TYRO3 signalling. TYRO3 knockdown also suppressed the expression of survivin in all the cell lines. TYRO3 knockdown potently suppressed TYRO3 mRNA expression but not that of AXL and MERTK. Furthermore, TYRO3 knockdown suppressed cyclin D1 mRNA expression, which is a downstream molecule of ERK. TYRO3 plays a role in leukaemia cell growth and is a potential therapeutic target for leukaemia.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
TYRO3 is a member of the TAM family (TYRO3, AXL, and MERTK) of receptor tyrosine kinases. While the roles of activated AXL and MERTK in the growth of leukaemia cells have been reported, the effect of TYRO3 has not been determined. Therefore, we examined the effects of TYRO3 knockdown on the growth of leukaemia cell lines.
MATERIALS AND METHODS
METHODS
Three human leukaemia cell lines (AA derived from pure erythroid leukaemia, OCI/AML2, and K562), which express TYRO3 protein were used in this study. To induce TYRO3 knockdown, small interfering RNA (siRNA) against TYRO3 was transfected using an electroporation system. Cell growth was assessed by a colorimetric assay. The expression levels and activation of various signalling proteins were examined by immunoblotting. Changes in comprehensive gene expression after TYRO3 knockdown were examined by microarray analysis.
RESULTS
RESULTS
TYRO3 knockdown suppressed cell growth in the leukaemia cell lines tested. Additionally, the knockdown suppressed phosphorylation of signal transducer and activator of transcription-3 in AA cells, and extracellular signal-regulated kinase (ERK) 1/2 in AA and OCI/AML2 cells; both are downstream molecules of TYRO3 signalling. TYRO3 knockdown also suppressed the expression of survivin in all the cell lines. TYRO3 knockdown potently suppressed TYRO3 mRNA expression but not that of AXL and MERTK. Furthermore, TYRO3 knockdown suppressed cyclin D1 mRNA expression, which is a downstream molecule of ERK.
CONCLUSION
CONCLUSIONS
TYRO3 plays a role in leukaemia cell growth and is a potential therapeutic target for leukaemia.
Identifiants
pubmed: 35346994
pii: 42/4/1757
doi: 10.21873/anticanres.15652
doi:
Substances chimiques
CCND1 protein, human
0
Proto-Oncogene Proteins
0
RNA, Small Interfering
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Cyclin D1
136601-57-5
MERTK protein, human
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
TYRO3 protein, human
EC 2.7.10.1
c-Mer Tyrosine Kinase
EC 2.7.10.1
Axl Receptor Tyrosine Kinase
0
AXL protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1757-1761Informations de copyright
Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.