Expression of p68 protein kinase and its prognostic significance during IFN-α therapy in patients with carcinoid tumours

Zhou, Ya‐Qun; Gobl, Anders; S, Wang; Jacobsen, M. B.; Janson, Eva Tiensuu; Haines, G. Kenneth; Radosevich, James A.; Öberg, Kjell

doi:10.1016/s0959-8049(98)00292-5

Cited by 21 publications

(27 citation statements)

References 37 publications

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“…In lymph node-negative rectal cancer, PKR expression levels were associated with disease recurrence (205). Further studies showed that increased expression of PKR correlates with better patient prognosis for certain tumors, and normal tissues tend to have lower PKR levels than their neoplastic counterparts (323,356,357,400).…”

Section: Role Of Pkr In Human Tumorigenesismentioning

confidence: 99%

Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action

García

Gil

Ventoso

et al. 2006

Microbiol Mol Biol Rev

702

731

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SUMMARY The double-stranded RNA-dependent protein kinase PKR is a critical mediator of the antiproliferative and antiviral effects exerted by interferons. Not only is PKR an effector molecule on the cellular response to double-stranded RNA, but it also integrates signals in response to Toll-like receptor activation, growth factors, and diverse cellular stresses. In this review, we provide a detailed picture on how signaling downstream of PKR unfolds and what are the ultimate consequences for the cell fate. PKR activation affects both transcription and translation. PKR phosphorylation of the alpha subunit of eukaryotic initiation factor 2 results in a blockade on translation initiation. However, PKR cannot avoid the translation of some cellular and viral mRNAs bearing special features in their 5′ untranslated regions. In addition, PKR affects diverse transcriptional factors such as interferon regulatory factor 1, STATs, p53, activating transcription factor 3, and NF-κB. In particular, how PKR triggers a cascade of events involving IKK phosphorylation of IκB and NF-κB nuclear translocation has been intensively studied. At the cellular and organism levels PKR exerts antiproliferative effects, and it is a key antiviral agent. A point of convergence in both effects is that PKR activation results in apoptosis induction. The extent and strength of the antiviral action of PKR are clearly understood by the findings that unrelated viral proteins of animal viruses have evolved to inhibit PKR action by using diverse strategies. The case for the pathological consequences of the antiproliferative action of PKR is less understood, but therapeutic strategies aimed at targeting PKR are beginning to offer promising results.

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Section: Role Of Pkr In Human Tumorigenesismentioning

confidence: 99%

Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action

García

Gil

Ventoso

et al. 2006

Microbiol Mol Biol Rev

702

731

View full text Add to dashboard Cite

show abstract

“…PKR levels have been inversely correlated with proliferative activity in Figure 5 Activation of PKR by IL3 deprivation. In IL3-dependent cells the withdrawal of IL3 results in the phosphorylation of RAX, a protein activator of PKR and subsequent eIF2a phosphorlyation, inhibition of protein synthesis and apoptosis di erent human tumors and tumor cell lines (Haines et al, 1996;Zhou et al, 1998;Shimanda et al, 1998). Human invasive ductal breast carcinomas have high levels of PKR and in several breast carcinoma cell lines PKR levels are high compared to those found in lines derived from normal breast (Haines et al, 1996;Savinova et al, 1999).…”

Section: Pkr Viral Mediated Apoptosis and Heat Shockmentioning

confidence: 99%

PKR; a sentinel kinase for cellular stress

1999

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“…Experiments examining cancers of the colon, breast, liver, and head and neck have shown a positive correlation between increasing PKR expression and more well-differentiated tumors (Haines et al, 1992(Haines et al, , 1993b(Haines et al, , 1996Shimada et al, 1998;Singh et al, 1995;Terada et al, 2000b). Increased expression of PKR has also been shown to correlate with better patient prognosis for certain tumors (Haines et al, 1993a;Zhou et al, 1998). Paradoxically, however, normal tissues tend to demonstrate lower PKR levels than their neoplastic counterparts (Singh et al, 1995;Haines et al, 1996;Shimada et al, 1998;Terada et al, 2000a,b).…”

Section: Introductionmentioning

confidence: 99%

Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR

et al. 2002

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The interferon-inducible, double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays key roles in regulation of cell growth and differentiation, and has been postulated as a tumor suppressor. Downstream effectors of PKR include the translation initiation factor, eIF2a, and the transcription factor, NF-kB. We found elevated levels of PKR protein, dsRNA-dependent PKR autophosphorylation activity, and phosphorylated eIF2a in melanoma cells compared to nontransformed melanocytes in culture. Treatment with interferon-a2b further induced PKR expression and activity. Immunohistochemical analysis of primary melanomas demonstrated minimal PKR immunoreactivity, but melanoma lymph node metastases expressed a high level of PKR protein. Furthermore, analysis of colon cancer specimens revealed that transformation from normal mucosa to adenomas and carcinomas was coincident with an increase in PKR expression. These data do not support the concept of PKR as a classic tumor suppressor but instead suggest that PKR upregulation occurs at defined steps in cancer progression, probably as a cellular response to neoplasia.

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Expression of p68 protein kinase and its prognostic significance during IFN-α therapy in patients with carcinoid tumours

Cited by 21 publications

References 37 publications

Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action

Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action

PKR; a sentinel kinase for cellular stress

Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR

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