LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 7; pp. 1961 - 1967
• Main Authors: Liu, C X, Musco, S, Lisitsina, N M, Forgacs, E, Minna, J D, Lisitsyn, N A
• Format: Journal Article
• Language: English
• Published: United States 01.04.2000
• Subjects: Amino Acid Sequence; Base Sequence; Carcinoma, Non-Small-Cell Lung - genetics; chromosome 2; Chromosome Mapping; Chromosomes, Human, Pair 2; Codon; Endocytosis; Gene Deletion; Genes, Tumor Suppressor; Genetic Markers; Homozygote; Humans; Low Density Lipoprotein Receptor-Related Protein-1; LRP-DIT gene; LRP1 protein; Lung Neoplasms - genetics; Molecular Sequence Data; Mutation, Missense; Open Reading Frames; Receptors, Immunologic - genetics; Tumor Cells, Cultured
• ISSN: 0008-5472

A variety of studies suggest that allelic losses at chromosome 2q are associated with aggressive behavior of various forms of human neoplasia. Using a probe to detect homozygous deletions on chromosome 2q21.2 in kidney and bladder cancer cell lines, we identified a new candidate tumor suppressor gene, lipoprotein receptor-related protein-deleted in tumors (LRP-DIT). The predicted LRP-DIT product of 4599 amino acids has extensive homology to a gigantic receptor, LRP1, which mediates endocytosis of multiple proteins from the cell surface. Homozygous deletions in LRP-DIT were detected in 17% (4 of 23) of non-small cell lung cancer (NSCLC) cell lines. The expression of only abnormal transcripts missing portions of the LRP-DIT sequence was demonstrated in an additional 30% (11 of 36) of NSCLC lines. Finally, a missense mutation at codon 3157 was detected in one of four NSCLC lines tested for the large open reading frame. In contrast, no LRP-DIT alterations were identified in a major fraction of SCLC cell lines, indicating that this gene is preferentially inactivated in one histological type of lung cancer. Our data suggest that inactivation of LRP-DIT occurs in at least 40% of NSCLC lines and thus may play an important role in tumorigenesis of NSCLCs.