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 language | English (US) |
|---|---|
| Pages (from-to) | 806-813 |
| Number of pages | 8 |
| Journal | Molecular Carcinogenesis |
| Volume | 47 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Loss of the eukaryotic initiation factor 3f in melanoma
AU - Doldan, Adriana
AU - Chandramouli, Anupama
AU - Shanas, Reneé
AU - Bhattacharyya, Achyut K
AU - Leong, Stanley P L
AU - Nelson, Mark A
AU - Shi, Jiaqi
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Eukaryotic initiation factor 3f
KW - Loss of heterozygosity
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=52649087857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52649087857&partnerID=8YFLogxK
U2 - 10.1002/mc.20436
DO - 10.1002/mc.20436
M3 - Article
C2 - 18381585
AN - SCOPUS:52649087857
VL - 47
SP - 806
EP - 813
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 10
ER -