The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in carcinoid tumors.
BACKGROUND
Interferon regulatory factor 1 (IRF-1) has been demonstrated to possess antiproliferative and tumor suppressor functions, on the contrary. IRF-2 has been suggested to induce oncogenetic effect in some cell lines, but not evaluated in tumor patients.


METHODS
In 35 carcinoid tumor patients, expressions of IRF-1 and IRF-2 were investigated by immunohistochemistry and their values were analyzed with clinical treatment response. In carcinoid tumor cell line, Bonl, effects of IFN-alpha on the expression of both IRF-1 and IRF-2 mRNAs and proteins were determined by Northern blot, RNase protection assays and Western blot analysis.


RESULTS
IFN-alpha up-regulated the expression of IRF-1 and IRF-2 both in vivo and in vitro. In carcinoid tumors, IFN-alpha treatment led to a significant increase in the expression of IRF-1 (P < 0.001) and IRF-2 (P < 0.001). Moreover, the IRFs induction was correlated with the clinical response of IFN-alpha treatment, although their baseline values were not predictive. In addition, expressions of IRF-1 and IRF-2 were significantly correlated with the p68 kinase expression (P = 0.032 and P = 0.0176, respectively) and the expression of IRF-1 protein was positively correlated with that of IRF-2 (r = 0.671, P = 0.0001) tested in the same specimens.


CONCLUSIONS
IRF-1 as well as IRF-2 have therapeutic implications in carcinoid tumors during treatment with interferon-alpha and IRFs induction might be used as indicators of response to treatment with interferon-alpha.
Zhou
Y
Y
Endocrine Oncology Unit of Internal Medicine, Uppsala University Hospital, Sweden.
Wang
S
S
Gobl
A
A
Oberg
K
K
D002276:Carcinoid Tumor / Q000378:metabolism / Q000628:therapy*; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use*; D010750:Phosphoproteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors