PMID- 11440637
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20181130
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 21
IP  - 6
DP  - 2001 Jun
TI  - Selective expression of nonsecreted interferon by an adenoviral vector confers 
      antiproliferative and antiviral properties and causes reduction of tumor growth 
      in nude mice.
PG  - 399-408
AB  - Replication-deficient adenoviruses expressing human interferon-alpha2b 
      (HuIFN-alpha2b) or the hybrid IFN-alpha2alpha1 or those with the secretory signal 
      deleted, whose express is driven by the alpha-fetoprotein (AFP) promoter, were 
      constructed and characterized. Synthesis of IFN protein and secretion or 
      intracellular retention were tested by Western blotting and immunoassay. 
      Expression of IFN by the recombinant adenoviruses was restricted to cells that 
      constitutively express AFP. In these cells, expression of both secreted and 
      nonsecreted recombinant IFN resulted in inhibition of cell proliferation, 
      resistance to viral infection, induction of major histocompatibility complex 
      (MHC) class I expression, increased apoptosis, and activation of an 
      IFN-stimulated response element (ISRE)-containing promoter. Also, the induction 
      of protein kinase R (PKR), increased phosphorylation of Stat1, and accumulation 
      of hypophosphorylated pRb were observed for both the secreted and nonsecreted 
      IFN, suggesting that the nonsecreted IFN may act through a similar pathway. Hep3B 
      cells, an AFP-positive line derived from a patient with hepatocellular carcinoma 
      (HCC), were injected subcutaneously (s.c.) into athymic nude mice to generate 
      established tumors. Intratumoral injection of recombinant adenoviruses expressing 
      secreted as well as the nonsecreted IFN caused suppression of tumor growth. As 
      the AFP promoter is activated in many HCC cells but is silent in normal cells, 
      these constructs may be useful in restricting IFN effects to the tumor cells 
      while reducing toxicity to the neighboring tissues.
FAU - Ahmed, C M
AU  - Ahmed CM
AD  - University of Florida, Department of Microbiology and Cell Science, Gainesville, 
      FL 32611-0700, USA. cmia_99@yahoo.com
FAU - Wills, K N
AU  - Wills KN
FAU - Sugarman, B J
AU  - Sugarman BJ
FAU - Johnson, D E
AU  - Johnson DE
FAU - Ramachandra, M
AU  - Ramachandra M
FAU - Nagabhushan, T L
AU  - Nagabhushan TL
FAU - Howe, J A
AU  - Howe JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (DNA Primers)
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 0 (alpha-Fetoproteins)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Apoptosis
MH  - Base Sequence
MH  - Cell Division
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - Encephalomyocarditis virus/immunology
MH  - Female
MH  - Gene Expression
MH  - Genetic Vectors
MH  - Humans
MH  - Interferon alpha-2
MH  - Interferon-alpha/*genetics/metabolism
MH  - Liver Neoplasms, Experimental/genetics/immunology/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Promoter Regions, Genetic
MH  - Recombinant Proteins
MH  - Signal Transduction
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - alpha-Fetoproteins/genetics
EDAT- 2001/07/07 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/07/07 10:00
PHST- 2001/07/07 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/07/07 10:00 [entrez]
AID - 10.1089/107999001750277871 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2001 Jun;21(6):399-408. doi: 
      10.1089/107999001750277871.