The abnormal activation of the epidermal growth factor (EGF) pathway is one of the most common findings in human cancer, and a number of molecular devices of laboratory and clinical relevance have been designed to block this transduction pathway. Because of the large number of cellular events that might be regulated through the activation of the four EGF receptor family members, it is possible that screening methodologies for the identification of new molecular targets working downstream of these pathways may provide new tools for cancer diagnosis and potentially prevention and therapy. In searching for EGF target genes, we have identified ERG 1.2, the mouse homolog of the solid tumor-associated gene STAG1. Both in humans and in mice, it belongs to a new gene family that can give origin to several protein isoforms through alternative splicing and/or multiple translation starts. Sequence analysis and experimental data suggest that ERG1.2 is likely to function as a membrane-bound protein interacting with downstream signaling molecules through, WW- and SH3-binding domains. ERG 1.2 is a cell-cycle-regulated gene, and both ERG 1.2 and STAG 1 are induced by EGF and other growth factors at the transcript and protein levels. Finally, we have demonstrated that, besides prostate cancer and renal cell carcinoma, STAG 1 was also overexpressed in breast and ovarian cancer cell lines and in breast primary tumors. Although in most cases STAG 1 overexpression is probably due to the abnormal activation of the EGF pathway, we have also demonstrated genetic amplification and rearrangement of its locus in one breast cancer cell line and one primary ovarian cancer, suggesting that STAG 1 might be a direct molecular target in the carcinogenetic process. Thus its overexpression might be regarded not only as a tumor marker but also as a potentially pathogenetic event.

EGF- and cell-cycle-regulated STAG1/PMEPA1 ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer / Giannini, Giuseppe; Ambrosini, Mi; DI MARCOTULLIO, Lucia; Cerignoli, F; Zani, Massimo; Mackay, Ar; Screpanti, Isabella; Frati, Luigi; Gulino, Alberto. - In: MOLECULAR CARCINOGENESIS. - ISSN 0899-1987. - STAMPA. - 38:4(2003), pp. 188-200. [10.1002/mc.10162]

EGF- and cell-cycle-regulated STAG1/PMEPA1 ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer

GIANNINI, Giuseppe;DI MARCOTULLIO, LUCIA;ZANI, Massimo;SCREPANTI, Isabella;FRATI, Luigi;GULINO, Alberto
2003

Abstract

The abnormal activation of the epidermal growth factor (EGF) pathway is one of the most common findings in human cancer, and a number of molecular devices of laboratory and clinical relevance have been designed to block this transduction pathway. Because of the large number of cellular events that might be regulated through the activation of the four EGF receptor family members, it is possible that screening methodologies for the identification of new molecular targets working downstream of these pathways may provide new tools for cancer diagnosis and potentially prevention and therapy. In searching for EGF target genes, we have identified ERG 1.2, the mouse homolog of the solid tumor-associated gene STAG1. Both in humans and in mice, it belongs to a new gene family that can give origin to several protein isoforms through alternative splicing and/or multiple translation starts. Sequence analysis and experimental data suggest that ERG1.2 is likely to function as a membrane-bound protein interacting with downstream signaling molecules through, WW- and SH3-binding domains. ERG 1.2 is a cell-cycle-regulated gene, and both ERG 1.2 and STAG 1 are induced by EGF and other growth factors at the transcript and protein levels. Finally, we have demonstrated that, besides prostate cancer and renal cell carcinoma, STAG 1 was also overexpressed in breast and ovarian cancer cell lines and in breast primary tumors. Although in most cases STAG 1 overexpression is probably due to the abnormal activation of the EGF pathway, we have also demonstrated genetic amplification and rearrangement of its locus in one breast cancer cell line and one primary ovarian cancer, suggesting that STAG 1 might be a direct molecular target in the carcinogenetic process. Thus its overexpression might be regarded not only as a tumor marker but also as a potentially pathogenetic event.
2003
growth factor; cell cycle regulation; breast cancer; ovarian cancer
01 Pubblicazione su rivista::01a Articolo in rivista
EGF- and cell-cycle-regulated STAG1/PMEPA1 ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer / Giannini, Giuseppe; Ambrosini, Mi; DI MARCOTULLIO, Lucia; Cerignoli, F; Zani, Massimo; Mackay, Ar; Screpanti, Isabella; Frati, Luigi; Gulino, Alberto. - In: MOLECULAR CARCINOGENESIS. - ISSN 0899-1987. - STAMPA. - 38:4(2003), pp. 188-200. [10.1002/mc.10162]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/256037
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