Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas.
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.
Fornaro
M
M
Istituto di Ricerche Farmacologiche Mario Negri--Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
Dell'Arciprete
R
R
Stella
M
M
Bucci
C
C
Nutini
M
M
Capri
M G
MG
Alberti
S
S
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D002277:Carcinoma / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D000071858:Epithelial Cell Adhesion Molecule; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger