Loss of the eukaryotic initiation factor 3f in pancreatic cancer

Adriana Doldan, Anupama Chandramouli, Reneé Shanas, Achyut K Bhattacharyya, John T Cunningham, Mark A Nelson, Jiaqi Shi

Research output: Contribution to journalArticle

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Abstract

Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in pancreatic cancer. Overexpression of eIF3f induces apoptosis in pancreatic cancer cells. The eIF3f gene is located at chromosome band region 11p15.4. Loss of 11p15.4 is a common event in many tumors including pancreatic cancer. In order to investigate the molecular mechanism of the decreased expression of eIF3f in pancreatic cancer, we performed loss of heterozygosity (LOH) analysis in 32 pancreatic cancer specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 71% to 93%. We also performed eIF3f gene copy number analysis using quantitative real time PCR to further confirm the specific allelic loss of eIF3f gene in pancreatic cancer. We demonstrated a statistically significant decrease of eIF3f gene copy number in pancreatic tumors compared with normal tissues with a tumor/normal ratio of 0.24. Furthermore, RNA in situ hybridization and tissue microarray immunohistochemistry analysis demonstrated that eIF3f expression is significantly decreased in human pancreatic adenocarcinoma tissues compared to normal pancreatic tissues. These data provides new insight into the understanding of the molecular pathogenesis of eIF3f during pancreatic tumorigenesis.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalMolecular Carcinogenesis
Volume47
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Eukaryotic Initiation Factors
Pancreatic Neoplasms
Loss of Heterozygosity
Gene Dosage
Neoplasms
Carcinogenesis
Tissue Array Analysis
Genes
Microsatellite Repeats
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Adenocarcinoma
Chromosomes
Immunohistochemistry
RNA
Apoptosis

Keywords

  • Apoptosis
  • Eukaryotic initiation factor 3f
  • Loss of heterozygosity
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Loss of the eukaryotic initiation factor 3f in pancreatic cancer. / Doldan, Adriana; Chandramouli, Anupama; Shanas, Reneé; Bhattacharyya, Achyut K; Cunningham, John T; Nelson, Mark A; Shi, Jiaqi.

In: Molecular Carcinogenesis, Vol. 47, No. 3, 03.2008, p. 235-244.

Research output: Contribution to journalArticle

Doldan, Adriana ; Chandramouli, Anupama ; Shanas, Reneé ; Bhattacharyya, Achyut K ; Cunningham, John T ; Nelson, Mark A ; Shi, Jiaqi. / Loss of the eukaryotic initiation factor 3f in pancreatic cancer. In: Molecular Carcinogenesis. 2008 ; Vol. 47, No. 3. pp. 235-244.
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