Growth-regulated cells, such as 3T3 mouse embryo fibroblasts (MEFs), require more than one growth factor for growth, usually the insulin-like growth factor I (IGF-I) in combination with either platelet-derived growth factor or epidermal growth factor. Singly, these growth factors cannot sustain the growth of 3T3 cells. However, if the IGF-I receptor (IGF-IR) is even modestly overexpressed, then IGF-I, by itself, stimulates the growth of MEFs in monolayer and makes them capable of forming colonies in soft agar. The granulin/epithelin precursor (GEP) has been identified as the only growth factor, thus far, that can stimulate by itself the growth of R- cells, a 3T3-like cell line in which the genes for the IGF-IR have been deleted. We have expressed GEP in R- cells and show that these cells can now grow in serum-free medium. GEP, however, cannot replace other functions of the IGF-IR, such as protection from apoptosis (anoikis) or transforming activity (colony formation in soft agar). GEP activates, in R- cells, the two signaling pathways that are known to be sufficient for IGF-I-mediated mitogenesis in cells overexpressing the IGF-IR, the mitogen-activated protein kinase and the phosphatidylinositol 3-kinase pathways. This may explain why GEP, by itself, can replace the IGF-IR for growth in monolayer cultures. It also confirms that, for transformation, other pathways must be activated besides the two pathways that are sufficient for mitogenesis.

Biological Activities and Signaling Pathways of the Granulin/Epithelin precursor / ZANOCCO MARANI, Tommaso; T, Bateman; A, Romano; G, Valentinis; B, ; Zhi, Heng; He, ; And, Baserga; R., BIOLOGICAL ACTIVITIES AND SIGNALING PATHWAYS OF THE GRANULINEPITHELIN PRECURSOR. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 59(20):(1999), pp. 5331-5340.

Biological Activities and Signaling Pathways of the Granulin/Epithelin precursor.

ZANOCCO MARANI, Tommaso;
1999

Abstract

Growth-regulated cells, such as 3T3 mouse embryo fibroblasts (MEFs), require more than one growth factor for growth, usually the insulin-like growth factor I (IGF-I) in combination with either platelet-derived growth factor or epidermal growth factor. Singly, these growth factors cannot sustain the growth of 3T3 cells. However, if the IGF-I receptor (IGF-IR) is even modestly overexpressed, then IGF-I, by itself, stimulates the growth of MEFs in monolayer and makes them capable of forming colonies in soft agar. The granulin/epithelin precursor (GEP) has been identified as the only growth factor, thus far, that can stimulate by itself the growth of R- cells, a 3T3-like cell line in which the genes for the IGF-IR have been deleted. We have expressed GEP in R- cells and show that these cells can now grow in serum-free medium. GEP, however, cannot replace other functions of the IGF-IR, such as protection from apoptosis (anoikis) or transforming activity (colony formation in soft agar). GEP activates, in R- cells, the two signaling pathways that are known to be sufficient for IGF-I-mediated mitogenesis in cells overexpressing the IGF-IR, the mitogen-activated protein kinase and the phosphatidylinositol 3-kinase pathways. This may explain why GEP, by itself, can replace the IGF-IR for growth in monolayer cultures. It also confirms that, for transformation, other pathways must be activated besides the two pathways that are sufficient for mitogenesis.
59(20)
5331
5340
Biological Activities and Signaling Pathways of the Granulin/Epithelin precursor / ZANOCCO MARANI, Tommaso; T, Bateman; A, Romano; G, Valentinis; B, ; Zhi, Heng; He, ; And, Baserga; R., BIOLOGICAL ACTIVITIES AND SIGNALING PATHWAYS OF THE GRANULINEPITHELIN PRECURSOR. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 59(20):(1999), pp. 5331-5340.
ZANOCCO MARANI, Tommaso; T, Bateman; A, Romano; G, Valentinis; B, ; Zhi, Heng; He, ; And, Baserga; R., BIOLOGICAL ACTIVITIES AND SIGNALING PATHWAYS OF THE GRANULINEPITHELIN PRECURSOR
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/460681
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