Loss of the eukaryotic initiation factor 3f in melanoma

Adriana Doldan, Anupama Chandramouli, Reneé Shanas, Achyut K Bhattacharyya, Stanley P L Leong, Mark A Nelson, Jiaqi Shi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. elF3 plays an important role in translation initiation. elF3f is the p47 subunit of the elF3 complex whose function in cancer is not clear. Initial studies from our group indicated that elF3f expression is decreased in melanoma. Overexpression of elF3f inhibits translation and induces apoptosis in melanoma cells. The elF3f gene is located at chromosome region 11p15.4. Loss of 11p15.4 is a common event in many tumors including melanoma. In order to investigate the molecular mechanism of the decreased expression of elF3f in melanoma, we performed loss of heterozygosity (LOH) analysis in 24 melanoma specimens using three microsatellite markers encompassing the elF3f gene. We showed that the prevalence of LOH ranged from 75% to 92% in melanoma. We also performed elF3f gene copy number analysis using quantitative real-time PCR to further confirm the specific allelic loss of the elF3f gene in melanoma. We demonstrated a statistically significant decrease of the elF3f gene copy number in melanoma compared with normal tissues with a tumor/normal ratio of 0.52. To further elucidate the somatic genetic alterations, we carried out mutation analysis covering the entire coding region and 5′UTR of the elF3f gene in melanoma tissues and cell lines. Despite some polymorphisms, we did not find any mutations. Furthermore, immunohistochemistry analysis demonstrated that elF3f protein expression is decreased in melanoma compared to benign nevi. These data provide new insight into the understanding of the molecular pathogenesis of elF3f during melanoma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)806-813
Number of pages8
JournalMolecular Carcinogenesis
Volume47
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Eukaryotic Initiation Factors
Melanoma
Loss of Heterozygosity
Gene Dosage
Genes
Carcinogenesis
Neoplasms
Mutation
Nevus
Microsatellite Repeats
Real-Time Polymerase Chain Reaction
Chromosomes
Immunohistochemistry

Keywords

  • Apoptosis
  • Eukaryotic initiation factor 3f
  • Loss of heterozygosity
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Loss of the eukaryotic initiation factor 3f in melanoma. / Doldan, Adriana; Chandramouli, Anupama; Shanas, Reneé; Bhattacharyya, Achyut K; Leong, Stanley P L; Nelson, Mark A; Shi, Jiaqi.

In: Molecular Carcinogenesis, Vol. 47, No. 10, 10.2008, p. 806-813.

Research output: Contribution to journalArticle

Doldan, A, Chandramouli, A, Shanas, R, Bhattacharyya, AK, Leong, SPL, Nelson, MA & Shi, J 2008, 'Loss of the eukaryotic initiation factor 3f in melanoma', Molecular Carcinogenesis, vol. 47, no. 10, pp. 806-813. https://doi.org/10.1002/mc.20436
Doldan, Adriana ; Chandramouli, Anupama ; Shanas, Reneé ; Bhattacharyya, Achyut K ; Leong, Stanley P L ; Nelson, Mark A ; Shi, Jiaqi. / Loss of the eukaryotic initiation factor 3f in melanoma. In: Molecular Carcinogenesis. 2008 ; Vol. 47, No. 10. pp. 806-813.
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