MOLECULAR-CLONING OF YEAST CYTOCHROME C-LIKE POLYPEPTIDE EXPRESSED INHUMAN LUNG-CARCINOMA - AN ANTIGEN RECOGNIZABLE BY LUNG CANCER-SPECIFIC HUMAN MONOCLONAL-ANTIBODY

We previously determined the amino acid sequence to the epitope (ATLFK TR) of cytochrome c from Candida krusei, which is cross-reactive to th e lung cancer-specific human monoclonal antibody HB4C5. Here we report that an antigen messenger RNA, which codes for a structure similar to the cytochrome c epitope, is expressed in the human lung adenocarcino ma A549. Sequencing analysis has revealed that this messenger RNA enco des a novel 190 amino acid polypeptide of 21-kDa containing an amino a cid sequence (ALLFFT) similar to the cytochrome c epitope, although th e total messenger RNA sequence is apparently different from the cytoch rome c messenger RNA. Western analysis indicated that an antibody-reco gnizable 21-kDa antigen which has the same molecular weight as the pre dicted polypeptide is expressed in the A549 adenocarcinoma. The in vit ro translated product of the antigen messenger RNA and synthesized ALL FFT peptide were both shown to be reactive with the monoclonal antibod y, indicating that this protein contains the epitope which enables A54 9 cells to specifically react with the antibody. The antigen mRNA was not expressed in non-transformed fibroblasts, suggesting that the anti gen mRNA expression was associated with cellular transformation. Also in part of the antigen nucleotide sequence, there was a segment that h ad about 90% homology to the long terminal repeat sequence (no. 297-47 5) of the human endogenous retrovirus HERV-K10, which was related to t he mouse mammary tumor virus.