Involvement of Interleukin-6 and Androgen Receptor Signaling in Pancreatic Cancer

Okitsu, Kohichiroh; Kanda, Tatsuo; Imazeki, Fumio; Yonemitsu, Yutaka; Ray, Ratna B.; Chang, Chawnshang; Yokosuka, Osamu

doi:10.1177/1947601910383417

Cited by 53 publications

(50 citation statements)

References 41 publications

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“…Androgen receptor (AR), belonging to nuclear receptors, is putatively involved in the development of cancers such as prostate cancer, HCC and pancreatic cancer [5][6][7]. Androgen as a ligand interacts with AR, leading to a suggested link between transcriptional control and physiology.…”

Section: Introductionmentioning

confidence: 99%

Androgen Receptor and Hepatocellular Carcinoma

Kanda¹

2013

J Gastrointest Dig Syst

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Section: Introductionmentioning

confidence: 99%

Androgen Receptor and Hepatocellular Carcinoma

Kanda¹

2013

J Gastrointest Dig Syst

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“…In pancreatic tissue, as well as in pancreatic adenocarcinoma, anabolic receptors have been detected [18]. As reported by Okitsu et al, those receptors may play an important role in carcinogenesis in pancreas, because the androgen receptor mediated transcription occurs in pancreatic cancer cell lines [19]. There has been a study of the effect of hormone therapy on the growth of human non-endocrine pancreatic adenocarcinoma xenografts in nude mice conducted, which indicated that the androgen testosterone stimulated tumor growth rate [3].…”

Section: Case Presentationmentioning

confidence: 60%

Anabolic steroid abuse and pancreatic insulinoma

Oleśna

Durczyński

Hogendorf

et al. 2016

MBS

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S u m m a r y B a c k g r o u n d . Anabolic steroid abuse is very common among bodybuilders and is related with a number of medical complications including tumorgenesis.C a s e r e p o r t . A 29-year-old male bodybuilder with one year history of abusing large doses of anabolic steroids presented with several episodes of neuroglycopenia with concomitant loss of consciousness. Results of imaging studies (USG, MRI, EUS) showed smooth-demarcated, focal solid lesion of 2cm in diameter in the body of the pancreas. The patient was characterized by Whipple's triad (hyperinsulinemia accompanied by hypoglycemia and signs of symptoms resolving upon glucose administration). No other disturbances were observed. The patient was qualified for the surgical treatment. Intraoperatively, tumor enucleation was performed. Postoperative time was complicated by pancreatic fistula that required reoperation involving Roux pancreaticojejunostomy.

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“…The lactogenic hormone prolactin, glucocortoicoids and insulin cooperate in the regulation of the β -casein gene promoter, and complex formation between the glucocorticoid receptor and Stat5 has been observed [21] . Many other transcription factor interactions were found, some of them acting sequentially, and help to explain the mechanisms of cellular transformation, e.g., in pancreatic cancer cells [32] . In these cells, IL-6 induces Stat3 and MAPK, which in turn activate the androgen receptor and the expression of androgen responsive genes.…”

Section: The Functional Consequences Of Stat Activation Are Dependentmentioning

confidence: 99%

The versatile regulation of cellular events by Jak-Stat signaling: from transcriptional control to microtubule dynamics and energy metabolism

Groner

Hennighausen

2012

Hormone Molecular Biology and Clinical Investigation

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The Stat proteins (signal transducers and activators of transcription) and their basic functions were discovered approximately 20 years ago in the context of investigations concerned with the transcriptional aspects of interferon regulation [1] , acute phase response in the liver [2] and lactogenic hormone regulation of genes in the mammary gland [3] . These diverse processes are regulated by a large number of cyto kines and growth factors, but a common principle has been discovered that describes how their signals are transduced from the extracellular milieu to the nucleus. The transmission of signals from the cell surface to the nucleus and their conversion into transcriptional programs and cellular phenotypes have long fascinated and intrigued researchers. The seeming simplicity of the signal transduction process mediated by Jak kinases and Stat transcription factors has inspired molecular biologists, developmental biologists, immunologists and cancer researchers. A large body of detail and surprising additional functions not envisaged by the original model have been added and attest to the versatility of these proteins.The structure of Stat family members is conserved with respect to the order of their functional domains. The latent form of the protein, present in the cytoplasm, can be activated by tyrosine phosphorylation to assume the role of a signal transducer and, subsequently, a nuclear transcription factor. Stats are able to transduce an activating external stimulus directly to the nucleus without the need of intermediary secondary messengers [4] . The functional domains comprise the amino terminal sequences enabling tetramerization, the coiled-coil domain mediating protein-protein interactions, the DNA binding domain, a linker domain, the SH2 domain crucial for dimerization and the carboxylterminal transactivation domain [5] .The general mechanisms leading to Stat activation were established early on. The signaling pathway originates with the extracellular binding of a specifi c ligand to its receptor, followed by the aggregation of the receptor on the cell membrane, the recruitment of Jak family kinases and their enzymatic activation, the phosphorylation of tyrosine residues in the cytoplasmic domains of the receptors and the recruitment of latent Stat molecules to these receptor domains. Phosphorylation of the monomeric Stat molecules induces their dimerization and translocation to the nucleus, where they recognize specifi c DNA response elements. Alternatively, Stats can be phosphorylated and activated by growth factor receptor tyrosine kinases or cytoplasmic tyrosine kinases [6] .An unexpected contributor to Stat3 activation has been found in the sphingosine-1-phosphate receptor-1 (S1PR1). This receptor is probably involved in the persistent activation of Stat3 found in tumor cells. The S1PR1 is a G protein coupled receptor, and the lysophospholipid sphingosine-1 -phosphate (S1P) acts as a ligand. The receptor is strongly expressed in tumor cells with activated Stat3, a transcription factor for th...

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Involvement of Interleukin-6 and Androgen Receptor Signaling in Pancreatic Cancer

Cited by 53 publications

References 41 publications

Androgen Receptor and Hepatocellular Carcinoma

Androgen Receptor and Hepatocellular Carcinoma

Anabolic steroid abuse and pancreatic insulinoma

The versatile regulation of cellular events by Jak-Stat signaling: from transcriptional control to microtubule dynamics and energy metabolism

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