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

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 c omponent of the eukaryotic translation initiation factor-3 (eIF3-p48). Int- 6/eIF3-p48 is expressed in all adult tissues which have been tested and ear ly in embryonic development. Int-6/eIF3-p48 has been highly conserved throu ghout evolution and the deduced amino acid sequence of the human gene produ ct is identical to the mouse protein. Viral insertions at the Int-6/eIF3-p4 8 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/eI F3-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. Tn this study we have examined Int-6/eIF3-p48 gene status and expression in two of the most comm on forms of cancer in humans, breast and lung tumors. Sixty-two breast carc inomas 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 brea st 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 LO H at the Int-6/eIF3-p48 locus was observed, Int-6/eIF3-p48 expression was n ot related to commonly used pathological parameters in breast cancer patien ts, while in NSCLC patients Int-6/eIF3-p48 expression was mainly seen in ad enocarcinomas (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 br east 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 m ay represent a new prognostic or predictive marker.