Reduced expression of INT-6/eIF3-p48 in human tumors.

  • Authors:
    • A Marchetti
    • F Buttitta
    • S Pellegrini
    • G Bertacca
    • R Callahan
  • View Affiliations

  • Published online on: Monday, January 1, 2001
  • Pages: 175-184 DOI: 10.3892/ijo.18.1.175
0

Abstract

The int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eIF3-p48). Int-6/eIF3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. Int-6/eIF3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. Viral insertions at the Int-6/eIF3-p48 locus in mouse mammary tumors result in production of chimeric Int-6/eIF3-p48/MMTV products that may act as dominant negative oncoproteins. Int-6/eIF3-p48 has also been identified as a human protein that binds to the human T-cell leukemia virus type I Tax oncoprotein. The role of Int-6/eIF3-p48 in human carcinogenesis is unknown at the present time. In this study we have examined Int-6/eIF3-p48 gene status and expression in two of the most common forms of cancer in humans, breast and lung tumors. Sixty-two breast carcinomas and 78 non-small cell lung carcinomas (NSCLC) were investigated. LOH at the Int-6/eIF3-p48 locus was observed in 5 (21%) of 24 informative breast tumors and 10 (29%) of 34 informative lung tumors. A reduced expression of Int-6/eIF3-p48 was seen in 23 (37%) of breast cancer samples and 24 (31%) of NSCLC samples. An association between Int-6/eIF3-p48 expression and LOH at the Int-6/eIF3-p48 locus was observed. Int-6/eIF3-p48 expression was not related to commonly used pathological parameters in breast cancer patients, while in NSCLC patients int-6/eIF3-p48 expression was mainly seen in adenocarcinomas (P<0.0001). In conclusion, our data show for the first time a decreased expression of Int-6/eIF3-p48 in a consistent portion of human breast and lung carcinomas, frequently associated with LOH at the Int-6/eIF3-p48 locus. Additional studies on larger series of tumor specimens with long-term follow-up are needed to determine whether Int-6/eIF3-p48 expression may represent a new prognostic or predictive marker.

Related Articles

Journal Cover

January 2001
Volume 18 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
Ranked #30/211 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Marchetti, A., Buttitta, F., Pellegrini, S., Bertacca, G., & Callahan, R. (2001). Reduced expression of INT-6/eIF3-p48 in human tumors.. International Journal of Oncology, 18, 175-184. http://dx.doi.org/10.3892/ijo.18.1.175
MLA
Marchetti, A., Buttitta, F., Pellegrini, S., Bertacca, G., Callahan, R."Reduced expression of INT-6/eIF3-p48 in human tumors.". International Journal of Oncology 18.1 (2001): 175-184.
Chicago
Marchetti, A., Buttitta, F., Pellegrini, S., Bertacca, G., Callahan, R."Reduced expression of INT-6/eIF3-p48 in human tumors.". International Journal of Oncology 18, no. 1 (2001): 175-184. http://dx.doi.org/10.3892/ijo.18.1.175