Phosphatidylinositol 3-kinase/nuclear factor- B signaling pathway is involved in the regulation of IGF-I on Fas-associated death domain-like interleukin-1-converting enzyme-inhibitory protein expression in cultured FRTL thyroid cells

Abstract

It is known that decreased apoptosis of thyrocytes may be involved in the formation of goiters in patients with Graves' disease, and growth factors are involved in regulating the size of the thyroid gland. The purpose of our study was to investigate mRNA and protein levels of an antiapoptotic protein, namely, Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). The results showed that in FRTL thyroid cells, treatment with IGF-I upregulated mRNA and protein levels of FLIP in a dose-dependant manner. While a specific nuclear factor-kB (NF-kB) inhibitor, BAY11-7082, blocked this effect. Further study demonstrated that IGF-I induced the DNA-binding activity of NF-kB in association with decreased expression of the NF-kB inhibitory protein IkBa. These findings implied that IGF-I increased FLIP expression by enhancing the activation of NF-kB in FRTL thyroid cells. Using a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, we also found that PI3K was involved in the pathway by which IGF-I activated NF-kB and increased FLIP expression. When treated with IGF-I and LY294002, decreased NF-kB DNA binding activity and increased expression of IkBa protein were detected in cultured thyroid cells, which further confirmed that NF-kB was under the control of the PI3K pathway. Taken together, our results suggest that IGF-I regulates the expression of FLIP in FRTL cells by activating the PI3K/NF-kB cascade.

Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

“…In turn, this leads to increased survival [29,31,49]. Here our findings suggest that the activation of NFκB downstream of DR3 may be independent of the TRAF2 pathway and would depend on the activation of the PI3K/Akt pathway, presumably downstream of a Src-dependent tyrosine phosphorylation of DR3 within the ITAM motif [50,51]. This possibility is in line with the finding that cell survival downstream of CD95/Fas is associated with its tyrosine phosphorylation, upstream of the activation of the PI3K/AKT pathway [26].…”

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

“…Phosphorylated Akt, but not EGFstimulated phosphorylated extracellular signal -regulated kinase, is associated with an increased proliferative index in prostate tumors (61). Indeed, IGF-I is capable of activating nuclear factor nB (via phosphoinositide-3-kinase and AKT) and thereby increasing the levels of FLIP message and protein in thyroid cancer cells (62), and has been directly implicated in prostate cancer progression (63). This suggests that the resistance of insulin-stimulated NRP cells to apoptosis, perhaps acting via sustained expression of FLIP, is reflective of changes in human tumors.…”

Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription

“…Rat liver samples ( n = 6) were collected from male Wistar rats or Sprague Dawley rats (weighing 200–220 g), obtained from Shandong University. The rat thyroid cell line FRTL-5 was cultured as we previously described [ 16 ]. Normal human thyroid tissues and FRTL-5 cells were used as positive controls.…”