Cloning of differentially expressed sequence tags from nickel-transformed human embryonic lung cells

Differential display polymerase chain reaction (DD-PCR) was used to analyze the differentially expressed genes from nickel-transformed human embryonic lung (HEL) cells (MRC-9 and IMR-90) and their control counterparts (non-tr eated). Two genes, MS515 and IC82, were confirmed by Northern blot analysis . MS515 was detected in control and nickel oxide (NiO)-transformed MRC-9 ce lls, as well as in non-small cell lung cancer (NSCLC) EBC-1 cells, while ve ry weak expression was observed in nickel subsulfide (Ni3S2)-transformed MR C-9 cells and small cell lung cancer (SCLC) SBC-2 cells. IC82 could not be detected in control IMR-90 cells, while it was expressed in EBC-1 cells and NiO- and Ni3S2-transformed IMR-90 cells. These findings indicate that indi vidual nickel compounds have their own target gene(s) in inducing lung canc er. Sequencing analyses showed that the MS515 gene shared a high degree of homology lover 80%) with the gene Mena, which is involved in actin polymeri zation. IC82 showed 99% homology with human chromosome 4 clone C0440E08 and a coding sequence in the brain. The roles of these two genes in nickel car cinogenesis will be discussed. (C) 2000 Elsevier Science Ireland Ltd. All r ights reserved.