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Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas
M Fornaro1, R Dell'Arciprete, M Stella
1Istituto di Ricerche Farmacologiche Mario Negri--Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
Abstract:
We have cloned by expression the cDNA encoding Trop-2, a cell-surface glycoprotein expressed by most human carcinomas. Formal proof of the identity of the clone is the hybridization to DNA and RNA from genomic TROP2 transfectants. TROP2 is a single-copy gene in human cells, hybridizes to a single 1.8-kb mRNA from expressing sources and encodes a 35,709 Da type-1 transmembrane protein with a single transmembrane domain. TROP2 is essentially identical to GA733-1. Thus, we have proven that GA733-1, for which a protein product had not been identified, is a functional gene. TROP2 is also homologous to TROP1/KSA/GA733-2, confirming the serological similarities between the 2 molecules. The homology between the Trop-1 and Trop-2 peptides is clustered in 2 extracytoplasmic domains and in the transmembrane/cytoplasmic region. Twelve cysteines and a potential cytoplasmic tyrosine phosphorylation site are also conserved. Trop-1 and Trop-2 are homologous to serum IGF-II-binding proteins and appear as signal transducers. Thus, they likely represent novel cell-surface receptors and may play a role in regulating the growth of carcinoma cells. On the other hand, we have found no evidence for a role of Trop-2 and Trop-1 as homophilic adhesion molecules.
Insights
Researchers cloned the Trop-2 gene, a protein found on most human carcinomas. This discovery identifies GA733-1 as a functional gene and suggests Trop-2 may regulate carcinoma cell growth.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Trop-2 is a cell-surface glycoprotein found on most human carcinomas.
- The protein product of the GA733-1 gene had not been previously identified.
Purpose of the Study:
- To clone the cDNA encoding Trop-2.
- To confirm the identity and function of the GA733-1 gene.
- To investigate the relationship between Trop-1 and Trop-2.
Main Methods:
- Cloning by expression of Trop-2 cDNA.
- Hybridization assays using DNA and RNA from genomic TROP2 transfectants.
- Sequence homology analysis between Trop-1 and Trop-2.
Main Results:
- The cDNA encoding Trop-2 was successfully cloned.
- Trop-2 is a single-copy gene encoding a 35,709 Da type-1 transmembrane protein.
- Trop-2 is identical to GA733-1, confirming it as a functional gene.
- Trop-2 is homologous to Trop-1/KSA/GA733-2, with conserved domains and features.
- Trop-1 and Trop-2 are homologous to IGF-II-binding proteins and act as signal transducers.
Conclusions:
- GA733-1 is a functional gene encoding the Trop-2 protein.
- Trop-2 and Trop-1 are novel cell-surface receptors potentially involved in regulating carcinoma cell growth.
- Trop-2 and Trop-1 do not appear to function as homophilic adhesion molecules.