Role of translocator protein in melanoma growth and progression

Рукша, Т. Г.; Aksenenko, M. B.; Papadopoulos, Vassilios

doi:10.1007/s00403-012-1294-5

Cited by 21 publications

(15 citation statements)

References 32 publications

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“…More studies, including high power light microscopy as well as electron microscopy, are needed to elucidate the microscopic observations of the present study. We are fully aware that a restricted number of other studies also show TSPO in other locations than mitochondria, including cell nuclei [7,46,47]. …”

Section: Discussionmentioning

confidence: 99%

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Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Yasin

Veenman

Singh

et al. 2017

IJMS

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It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 min, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with real-time, reverse transcriptase (RT) PCR. At the time points of 15, 30, 45, and 60 min, as well as 3 and 24 h of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 h of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

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Section: Discussionmentioning

confidence: 99%

“…While TSPO location in mitochondria has received a lot of attention, it is also known that TSPO can be present in perinuclear locations [7,46,47,48]. To investigate this further, we applied confocal microscopy to triple labeling of nuclei, mitochondria, and TSPO.…”

Section: Introductionmentioning

confidence: 99%

Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Yasin

Veenman

Singh

et al. 2017

IJMS

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“…Furthermore, TSPO protein expression correlated positively with disease progression of some cancers, including oral cancers [35], brain cancers [24], colon cancers [29] and breast cancers [19,30]. The prognosis of some cancers also correlates negatively with the expression of TSPO [29,36,37]. …”

Section: Introductionmentioning

confidence: 99%

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Bhoola

Mbita

Hull

et al. 2018

IJMS

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TSPO is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed that the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer, and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney, and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of Tspo mRNA is not necessarily a good diagnostic biomarker in most cancers with changes not being large enough to be significantly different when detected by in situ hybridisation.

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Section: Introductionmentioning

confidence: 99%

Classical and Novel TSPO Ligands for the Mitochondrial TSPO can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Yasin

Veenman

Singh

et al. 2017

Preprint

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Abstract:It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

show abstract

Role of translocator protein in melanoma growth and progression

Cited by 21 publications

References 32 publications

Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

Classical and Novel TSPO Ligands for the Mitochondrial TSPO can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

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