Distinct genetic abnormalities (loss-of-function mutationsof APC and p53 and oncogenic activation of Ki-ras) are as-sociated with specific stages of the sporadic, most commontypes of colorectal tumors. However, the inability to main-tain primary colon epithelial cells in culture has hinderedthe analysis of the pathogenetic role of these abnormalitiesin colorectal tumorigenesis. We have now established pri-mary cultures of epithelial cells from the colon crypts ofp53-deficient mice; these cells are nontumorigenic as indi-cated by their failure to form colonies in soft agar and togrow as tumors in immunodeficient SCID mice and in im-munocompetent syngeneic hosts. Upon ectopic expressionof an activated Ki-ras gene, p53-deficient colon epithelialcells form colonies in soft agar and highly invasive subcuta-neous tumors in both immunodeficient and immunocompe-tent mice. Ectopic expression of wild-type p53, but not of aDNA-binding–deficient mutant, markedly suppressed thecolony-forming ability of the Ki-ras–transformed p53-defi-cient epithelial cells. Together, these findings establish afunctional synergism in colorectal tumorigenesis dependenton the effects of an oncogenic Ki-ras in a p53-deficientbackground. This model of tumorigenic conversion of colonepithelial cells might be useful to identify genetic changesassociated with disease progression and to evaluate thetherapeutic response to conventional and novel anticancerdrugs.

Tumorigenic conversion of p53 deficient colon epithelial cells by an activated Ki-ras gene / Sevignani, C; Wlodarski, P; Kirillova, J; Mercer, We; Danielson, Kg; Iozzo, Rv; Calabretta, Bruno. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 101:(1998), pp. 1572-1580.

Tumorigenic conversion of p53 deficient colon epithelial cells by an activated Ki-ras gene

CALABRETTA, Bruno
1998

Abstract

Distinct genetic abnormalities (loss-of-function mutationsof APC and p53 and oncogenic activation of Ki-ras) are as-sociated with specific stages of the sporadic, most commontypes of colorectal tumors. However, the inability to main-tain primary colon epithelial cells in culture has hinderedthe analysis of the pathogenetic role of these abnormalitiesin colorectal tumorigenesis. We have now established pri-mary cultures of epithelial cells from the colon crypts ofp53-deficient mice; these cells are nontumorigenic as indi-cated by their failure to form colonies in soft agar and togrow as tumors in immunodeficient SCID mice and in im-munocompetent syngeneic hosts. Upon ectopic expressionof an activated Ki-ras gene, p53-deficient colon epithelialcells form colonies in soft agar and highly invasive subcuta-neous tumors in both immunodeficient and immunocompe-tent mice. Ectopic expression of wild-type p53, but not of aDNA-binding–deficient mutant, markedly suppressed thecolony-forming ability of the Ki-ras–transformed p53-defi-cient epithelial cells. Together, these findings establish afunctional synergism in colorectal tumorigenesis dependenton the effects of an oncogenic Ki-ras in a p53-deficientbackground. This model of tumorigenic conversion of colonepithelial cells might be useful to identify genetic changesassociated with disease progression and to evaluate thetherapeutic response to conventional and novel anticancerdrugs.
1998
101
1572
1580
Tumorigenic conversion of p53 deficient colon epithelial cells by an activated Ki-ras gene / Sevignani, C; Wlodarski, P; Kirillova, J; Mercer, We; Danielson, Kg; Iozzo, Rv; Calabretta, Bruno. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 101:(1998), pp. 1572-1580.
Sevignani, C; Wlodarski, P; Kirillova, J; Mercer, We; Danielson, Kg; Iozzo, Rv; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/449850
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