Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
| Autor: | Larissa Brussa Reis, Mariane da Cunha Jaeger, Patricia Ashton-Prolla, Clévia Rosset, Cristina Brinckmann Oliveira Netto, Rafael Roesler, Eduardo C. Filippi-Chiela, Caroline Brunetto de Farias, Ivaine Tais Sauthier Sartor |
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| Rok vydání: | 2021 |
| Předmět: |
Esclerose tuberosa
mTOR inhibitors congenital hereditary and neonatal diseases and abnormalities Ciclo celular Cell Autofagia Sobrevivência celular mTORC1 QH426-470 Biology Loss of heterozygosity Autophagy Genetics medicine neurocutaneous disorder Rapamycin neoplasms Molecular Biology Cell cycle Cellular Molecular and Developmental Genetics nervous system diseases medicine.anatomical_structure Alvo mecanístico do complexo 1 de rapamicina Tuberous Sclerosis Complex Cancer research TSC1 TSC2 Haploinsufficiency |
| Zdroj: | Genetics and Molecular Biology, Vol 44, Iss 4 (2021) Genetics and Molecular Biology Genetics and Molecular Biology, Volume: 44, Issue: 4, Article number: e20200475, Published: 01 OCT 2021 Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
| ISSN: | 1678-4685 1415-4757 |
| DOI: | 10.1590/1678-4685-gmb-2020-0475 |
| Popis: | Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development. Flow cytometry analyses were performed to evaluate cell viability, cell cycle and autophagy in non-tumor primary TSC cells with different heterozygous mutations and in control cells without TSC mutations, before and after treatment with rapamycin (mTORC1 inhibitor). We did not observe differences in cell viability and cell cycle between the cell groups. However, autophagy was reduced in mutated cells. After rapamycin treatment, mutated cells showed a significant increase in the autophagy process (p=0.039). We did not observe differences between cells with distinct TSC mutations. Our main finding is the alteration of autophagy in non-tumor TSC cells. Previous studies in literature found autophagy alterations in tumor TSC cells or knock-out animal models. We showed that autophagy could be an important mechanism that leads to TSC tumor formation in the haploinsufficiency state. This result could guide future studies in this field. |
| Databáze: | OpenAIRE |
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