Type of Bacterial Copper Zinc Lead No culture 1 DPMC1 5.102 8.082 10.160 2 DPMC2 7.290 7.748 10.582 3 DPMC3 8.102 5.780 8.020 4 DPMC4 7.956 10.918 7.810 5 DPMC5 7.028 10.748 7.688 6 TSC1 9.160 6.796 6.582 7 TSC2
9.580 10.510 8.802 8 TSC3 8.218 7.494 6.788 9 TSC4 5.782 5.536 5.780 Fig.
Quantitative RT -PCR reveals tuberous sclerosis gene, TSC2
, mRNA degradation following cryopreservation in the human preimplantation embryo.
Drosophila Tsc1 functions with Tsc2
to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.
Louis, "AKT activation in human glioblastomas enhances proliferation via TSC2
and S6 kinase signaling," Cancer Research, vol.
Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 (coding hamartin) or TSC2
(coding tuberin) genes.
In addition to those actions that are susceptible to developing resistance upon obesity and T2D, insulin, through the sequential PI3K-Akt activation, inhibitory phosphorylation of the complex tuberous sclerosis complex 1/2 (TSC1/ TSC2
), and activation of Ras homolog enriched in the brain (Rheb), activates the mechanistic target of rapamycin complex 1 (mTORC1), which in turn promotes protein synthesis by phosphorylating the ribosomal protein S6K and eukaryotic translational initiation factor 4E-binding protein 1 (4E-BP), among many other processes .
Akt can be phosphorylated and activated by mTORC2 to promote cell survival and proliferation through FoxO1/3a, GSK3[beta], and TSC2
downstream of Akt.
Mutations in TSC1, TSC2
, and MTOR are associated with response to rapalogs in patients with metastatic renal cell carcinoma.
Customized NimbleGen array (NimbleGen, Roche, USA) was used to capture and enrich 27,000b target region (all exons and flanking 100 bp) of TSC1 and TSC2
In our patient's future off springs, we plan to conduct antenatal screening as multiple imaging modalities can confirm in utero diagnosis of TCS.6 An anomaly scan done in 2nd trimester can identify major structural anomalies in about 60% cases, including fetal cardiac rhabdomyomas, polycystic kidney disease, or CNS lesions as seen in TSC.7 Genetic testing for TSC1 and TSC2
having more than 90% sensitivity is commercially available in developed countries of the world but rarely available and very costly in developing countries.
Genes Tested AtP ALK APC ATM BAP1 BRCA2 BRIP1 BUB1B CDC73 CDH1 CEP57 CHEK2 CYLD DDB2 DICER1 ERCC3 ERCC4 ERCC5 EXT1 EXT2 FANCD2 FANCE FANCF FANCG FANCI GATA2 GPC3 HNF1A HOXB13 HRAS MLH1 MHS2 MSH6 MUTYH NBN PHOX2B PMS1 PMS2 PPM1D PRF1 RAD51D RBI RECQL4 RET RHBDF2 SDHC SDHD SLX4 SMAD4 SMARCA4 TP53 TSC1 TSC2
VHL WT1 BARD1 BLM BMPR1A BRCA1 CDK4 CDKN1C CDKN2A CEBPA DI53L2 EGFR EPCAM ERCC2 EZH2 FANCA FANCB FANCC FANCL FANCM FH FLCN KIT MAX MEN1 MET NF1 NF2 NSD1 PALB2 PRKAR1A PTCH1 PTEN RAD51C RUN XI SBDS SDHAF2 SDHB SMARCB1 STK11 5UFU TMEM127 WRN XPA XPC This chart shows all 98 cancer susceptible genes included in this new test.
The disorder remained relatively obscure until the early 2000s, when the molecular mechanisms of TSC were identified, showing that the two proteins directly affected, TSC1 and TSC2
, are key regulators in a fundamental intracellular signalling pathway, the mTOR (mammalian target of rapamycin) pathway.