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LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines
C X Liu1, S Musco, N M Lisitsina
1Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Abstract:
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.
Insights
A new tumor suppressor gene, lipoprotein receptor-related protein-deleted in tumors (LRP-DIT), was identified. Inactivation of LRP-DIT occurs in at least 40% of non-small cell lung cancer (NSCLC) lines, suggesting its role in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Allelic losses at chromosome 2q are linked to aggressive human neoplasia.
- A novel candidate tumor suppressor gene, LRP-DIT, was investigated.
- LRP-DIT shares homology with LRP1, a receptor involved in endocytosis.
Purpose of the Study:
- To identify and characterize a novel tumor suppressor gene involved in non-small cell lung cancer (NSCLC).
- To investigate the role of LRP-DIT in NSCLC tumorigenesis.
Main Methods:
- Utilized probes to detect homozygous deletions at chromosome 2q21.2 in cancer cell lines.
- Analyzed LRP-DIT gene alterations including deletions, abnormal transcripts, and mutations in NSCLC and SCLC cell lines.
- Compared LRP-DIT alterations between NSCLC and SCLC to determine tissue specificity.
Main Results:
- Identified homozygous deletions in LRP-DIT in 17% of NSCLC cell lines.
- Detected abnormal LRP-DIT transcripts in 30% of NSCLC lines.
- Found a missense mutation in one NSCLC line and no LRP-DIT alterations in SCLC lines, indicating preferential inactivation in NSCLC.
Conclusions:
- LRP-DIT inactivation occurs in at least 40% of NSCLC lines.
- LRP-DIT may play a significant role in the tumorigenesis of NSCLC.
- The gene is preferentially inactivated in NSCLC compared to SCLC.