title: Upregulation of Trop-2 quantitatively stimulates human cancer growth.
abstract: Trop-2 is a calcium signal transducer that is associated with transformed cell growth in experimental systems. However, its role in human cancer remains essentially unknown. In this study, we profiled Trop-2 expression in normal human tissues at the mRNA and protein levels. We then systematically compared Trop-2 mRNA and protein levels in tumours with their tissues of origin. We find that Trop-2 expression is invariably upregulated in tumours, regardless of baseline expression in normal tissues, which suggests a corresponding selective advantage. Thus, we investigated the outcome of Trop-2 upregulation on tumour growth. Overexpression of wild-type Trop-2 was shown to be necessary and sufficient to drive cancer growth in a widely invariant manner across cell type and species. Upregulation of Trop-2 was shown to quantitatively stimulate tumour growth, as proportional to expression levels in vivo, and tumour cell growth was abrogated by somatic knockdown of Trop-2 expression. On the other hand, we found no evidence of tumour-associated TROP2 mutations, nor of TROP2 induction of oncogenic transformation per se. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth.
authors.affiliation: Unit of Cancer Pathology, Department of Oncology and Experimental Medicine, CeSI, Foundation University 'G. d'Annunzio', Chieti Scalo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Trerotola
authors.forename: P
authors.initials: P
authors.lastname: Cantanelli
authors.forename: E
authors.initials: E
authors.lastname: Guerra
authors.forename: R
authors.initials: R
authors.lastname: Tripaldi
authors.forename: A L
authors.initials: AL
authors.lastname: Aloisi
authors.forename: V
authors.initials: V
authors.lastname: Bonasera
authors.forename: R
authors.initials: R
authors.lastname: Lattanzio
authors.forename: R
authors.initials: R
authors.lastname: de Lange
authors.forename: U H
authors.initials: UH
authors.lastname: Weidle
authors.forename: M
authors.initials: M
authors.lastname: Piantelli
authors.forename: S
authors.initials: S
authors.lastname: Alberti
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C499380:TACSTD2 protein, human