دورية أكاديمية
Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state
| العنوان: | Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state |
|---|---|
| المؤلفون: | Clévia Rosset, Mariane da Cunha Jaeger, Eduardo Filippi-Chiela, Larissa Brussa Reis, Ivaine Taís Sauthier Sartor, Cristina Brinckmann Oliveira Netto, Caroline Brunetto de Farias, Rafael Roesler, Patricia Ashton-Prolla |
| المصدر: | Genetics and Molecular Biology, Vol 44, Iss 4 (2021) |
| بيانات النشر: | Sociedade Brasileira de Genética |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Autophagy, mTOR inhibitors, neurocutaneous disorder, Rapamycin, Tuberous Sclerosis Complex, Genetics, QH426-470 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1678-4685 |
| العلاقة: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572021000600701&tlng=enTest; https://doaj.org/toc/1678-4685Test; https://doaj.org/article/fe7d672f066a416495abc777371618deTest |
| DOI: | 10.1590/1678-4685-gmb-2020-0475 |
| الإتاحة: | https://doi.org/10.1590/1678-4685-gmb-2020-0475Test https://doaj.org/article/fe7d672f066a416495abc777371618deTest |
| رقم الانضمام: | edsbas.7534C601 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16784685 |
|---|---|
| DOI: | 10.1590/1678-4685-gmb-2020-0475 |