Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.
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PMID:Comparative immunohistochemical analysis of ochratoxin A tumourigenesis in rats and urinary tract carcinoma in humans; mechanistic significance of p-S6 ribosomal protein expression. 2310 73

The mammalian target of rapamycin (TOR) has been implicated in the control of different stressors, growth factors, nutrients and hormones, participating in the control of key cellular functions. Controlling this many pathways poses mTOR signalling as a potential new target in new treatment strategies for multiple cancer types. mTOR components could potentially mislocated in tumour cells, which could lead to activation of signalling pathway that should not be active. Therefore, we aimed to show localisation of mTOR signal proteins in testicular seminoma. Tumoural testicular tissues were obtained from 10 patients with unilateral classic seminoma undergoing to therapeutic orchidectomy and compared with control human testicular tissues. Upon immunohistochemical evaluation, we detected mTOR and p-mTOR (serine 2448), P70S6K, p-P70S6K, PKCalpha and p-PKCalpha, CD36 and MAPLC3 proteins in the cytoplasm of Sertoli cells in the seminiferous tubules. We also showed cytoplasmic perinuclear staining in seminoma cells. This study demonstrated the interaction of mTOR signalling pathway and testicular seminoma by showing intense cytoplasmic mTOR pathway proteins immunoreactivity in the seminoma, for the first time in humans. Therefore, we suggested that mTOR signalling components could create new clinical targets for treatment of testicular seminoma patients and male infertility in the future.
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PMID:mTOR expression in human testicular seminoma. 2664 40

Human testis development-related gene 1 (TDRG1) is a recently identified gene that is expressed exclusively in the testes and promotes the development of testicular germ cell tumors. In this study, the role of TDRG1 in the development of testicular seminoma, which is the most common testicular germ cell tumor, was further investigated. Based on polymerase chain reaction, Western blotting, and immunohistochemistry tests, both gene and protein expression levels of TDRG1 were significantly upregulated in testicular seminoma tissues compared with normal testicular tissues. Additionally, the levels of phosphoinositide-3 kinase (PI3K)/p110 and Akt phosphorylation were dramatically upregulated in testicular seminoma tissues. Accordingly, in our cell experiment, seminoma TCam-2 cells were subjected to different treatments: the TDRG1 knockout, TDRG1 overexpression, PI3K inhibition (LY294002 administration), or PI3K activation (insulin-like growth factor-1 administration). Cell proliferation, the proliferation index, apoptosis rate, cell adhesive capacity, and cell invasion capability were assessed. Cells with both TDRG1 knockout and PI3K inhibition exhibited decreased cell proliferation, proliferation indexes, cell adhesion capacity, and cell invasion capability and increased apoptosis rates. Most of these effects were reversed by TDRG1 overexpression or PI3K activation, indicating that both TDRG1- and PI3K-mediated signaling promote proliferation and invasion of testicular seminoma cells. The knockout of TDRG1 significantly decreased the phosphorylation levels of PI3K/p85, PI3K/p110, Akt, and mammalian target of rapamycin (mTOR; Ser(2448)). Except for PI3K/p110, TDRG1 overexpression had the opposite effects on phosphorylation levels. Phosphorylated mTOR at Ser(2481) and Thr(2446) was not affected by TDRG1 or PI3K in our tests. Thus, these results indicate that TDRG1 promotes the development and migration of seminoma cells via the regulation of the PI3K/Akt/mTOR signaling pathway; this contributes to an understanding of the precise mechanisms underlying the development and migration of seminomas and lays a theoretical foundation for the development of appropriate therapies.
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PMID:TDRG1 functions in testicular seminoma are dependent on the PI3K/Akt/mTOR signaling pathway. 2685 90