Trop-1 are conserved growth stimulatory molecules that mark early stages of tumor progression.
BACKGROUND
Trop-1 is a cell-cell adhesion regulatory molecule that is overexpressed by a large fraction of tumors in man.


METHODS
To identify fundamental, conserved functional features of Trop-1 in transformed cells, a search was performed for evolutionarily conserved structure, expression patterns, and function by gene cloning, DNA array and serial analysis of gene expression (SAGE), Northern and Western blotting, flow cytometry, and immunohistochemistry of sequential stages of tumor progression in experimental systems and in man.


RESULTS
TROP1 genes demonstrate conserved structure and promoter regions with parallel expression patterns (high expression in the small intestine and colon; lower expression in prostate, thyroid, salivary glands, breast, kidney, lung, liver, and spleen; very low levels in skin and stomach; no expression in heart, muscle, and brain). Progenitor cells of different tissues were shown to express Trop-1. Hence, the expression and functional role of Trop-1 were analyzed at successive stages of tumor progression in vitro and in vivo. The findings show that Trop-1 is expressed at early stages of tumor development, eg, in dysplastic lesions and immortalized cells, is sufficient to stimulate cell growth of expressing transformed cells, and is required for tumor growth in vivo.


CONCLUSIONS
The findings identify Trop-1 as a novel determinant of cell growth at early stages of tumor development and as a marker of early stages of development in normal tissues and in cancer, making this molecule a candidate for novel diagnostic and therapeutic procedures.
Zanna
Paola
P
Laboratory of Experimental Oncology, Consorzio Mario Negri Sud, S.M. Imbaro, Chieti, Italy.
Trerotola
Marco
M
Vacca
Giovanna
G
Bonasera
Veronica
V
Palombo
Barbara
B
Guerra
Emanuela
E
Rossi
Cosmo
C
Lattanzio
Rossano
R
Piantelli
Mauro
M
Alberti
Saverio
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004247:DNA; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D012689:Sequence Homology, Nucleic Acid
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D034741:RNA, Small Interfering; D004247:DNA