Over-expression of interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes

Abstract

Background-Over-expression of IL-6 has been implicated in cholangiocarcinoma growth but the cellular mechanisms involved are unknown. Our aims were to assess the mechanisms by which overexpression of IL-6 promotes transformed cell growth in malignant cholangiocytes.

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

“…Still, we have not found any data on Epo expression and signaling in human cholangiocarcinoma www.wjgnet.com Smirnova OV et al JAK-STAT and cholangiocarcinoma cell leukemia-1 (mcl-1) mRNA and protein expression which is a key member of the antiapoptotic Bcl-2 protein family [107,110] . Disruption of IL-6 signaling at different levels diminishes Mcl-1 promoter activity, its mRNA and protein level in human cholangiocarcinoma cell lines.…”

“…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] .…”

The MicroRNA let-7a Modulates Interleukin-6-dependent STAT-3 Survival Signaling in Malignant Human Cholangiocytes

“…: 614-293-6202; Fax: 614-293-0861; E-mail: patel.lab@gmail.com. 2 The abbreviations used are: IL-6, interleukin-6; miRNA, micro-RNA; NF2, neurofibromatosis 2; Stat-3, signal transducers and activators of transcription-3; MAPK, mitogen-activated protein kinase; UTR, untranslated region; PARP, poly(ADP-ribose) polymerase-1; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling; HRS, hepatocyte growth factor regulated tyrosine kinase substrate. …”

“…IL-6 has been implicated in tumor growth in many of these tumors, and elevated IL-6 expression has been associated with poor outcomes and resistance to chemotherapy (1). Experimentally, growth of prostate cancer and cholangiocarcinoma xenografts in athymic mice has been shown to be increased by enforced expression of IL-6 by activation of cell survival signaling (2,3). The mechanisms by which IL-6 promotes cell survival in cancers are of considerable interest because they may be therapeutically targeted.…”

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.…”