Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26041883
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Thyroid hormone and anti-apoptosis in tumor cells
#MMPMID26041883
Lin HY
; Glinsky GV
; Mousa SA
; Davis PJ
Oncotarget
2015[Jun]; 6
(17
): 14735-43
PMID26041883
show ga
The principal secretory product of the thyroid gland, L-thyroxine (T4), is
anti-apoptotic at physiological concentrations in a number of cancer cell lines.
Among the mechanisms of anti-apoptosis activated by the hormone are interference
with the Ser-15 phosphorylation (activation) of p53 and with TNF?/Fas-induced
apoptosis. The hormone also decreases cellular abundance and activation of
proteolytic caspases and of BAX and causes increased expression of X-linked
inhibitor of apoptosis (XIAP). The anti-apoptotic effects of thyroid hormone
largely are initiated at a cell surface thyroid hormone receptor on the
extracellular domain of integrin ?v?3 that is amply expressed and activated in
cancer cells. Tetraiodothyroacetic acid (tetrac) is a T4 derivative that, in a
model of resveratrol-induced p53-dependent apoptosis in glioma cells, blocks the
anti-apoptotic action of thyroid hormone, permitting specific serine
phosphorylation of p53 and apoptosis to proceed. In a nanoparticulate formulation
limiting its action to ?v?3, tetrac modulates integrin-dependent effects on gene
expression in human cancer cell lines that include increased expression of a
panel of pro-apoptotic genes and decreased transcription of defensive
anti-apoptotic XIAP and MCL1 genes. By a variety of mechanisms, thyroid hormone
(T4) is an endogenous anti-apoptotic factor that may oppose chemotherapy-induced
apoptosis in ?v?3-expressing cancer cells. It is possible to decrease this
anti-apoptotic activity pharmacologically by reducing circulating levels of T4 or
by blocking effects of T4 that are initiated at ?v?3.
free
free
free
