Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

“…SOCS3 negative cholangiocarcinoma (as well as cholangiocarcinoma lines) samples are characterized by extensive methylation of SOCS3 promoter as compared with nontumor tissue. Treatment with demethylating agent restores IL-6 induction of SOCS3 leading to termination of phosphorylated STAT3 response, reduction of cholangiocarcinoma cells level of Mcl-1, and sensitization of cholangiocarcinoma cells to Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL)-mediated apoptosis [111,112] . In the 5′-flanking region of human HGF gene cis-acting STAT element has been found.…”

“…Mcl-1 promotor has STAT3 binding site. STAT3 site-directed mutagenesis decreases Mcl-1 promotor activity [111] .…”

“…Table 3 a number of genes involved in cholangiocarcinoma growth signaling, cell cycle regulation, and apoptosis inhibition possess candidate STAT3-, STAT5-, and STAT-1-binding sites in their promoters. Prl and IL-6 induced STAT5 and STAT3 activation is essential for up-regulation of their transcription activity in different tumor types and leads mainly to tumor progression [2,16,86,107,[110][111][112]155,156] .…”

Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic lymphocytic leukemia

“…3,4 The median percentage of tumor lymphocytes in patient samples was 74% (37-99%, range) as assessed with immunophenotype analysis (n ¼ 69). Residual normal cells did not significantly affect the determination of MCL-1 mRNA, since there was no difference in MCL-1 levels between the samples with 474% tumor purity and those with o74% purity (Kruskall-Wallis test, P ¼ 0.41, NS).…”

Piercing the armor of hepatobiliary cancer: Bcl-2 homology domain 3 (BH3) mimetics and cell death

“…2,3 Likewise, although information is more limited, the same trend of signaling-induced alterations in Bcl-2 family member expression appears to be true for cholangiocarcinoma. [4][5][6] In this regard, hepatobiliary cancers are like most other malignancies and are addicted to Bcl-2 family proteins. This article discusses specific recent advances in overcoming resistance to apoptosis by antiapoptotic Bcl-2 family proteins, especially as it relates to targeting these proteins for treatment of hepatobiliary malignancies.…”