Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
J Clin Invest ; 101(8): 1572-80, 1998 Apr 15.
Article in English | MEDLINE | ID: mdl-9541486

ABSTRACT

Distinct genetic abnormalities (loss-of-function mutations of APC and p53 and oncogenic activation of Ki-ras) are associated with specific stages of the sporadic, most common types of colorectal tumors. However, the inability to maintain primary colon epithelial cells in culture has hindered the analysis of the pathogenetic role of these abnormalities in colorectal tumorigenesis. We have now established primary cultures of epithelial cells from the colon crypts of p53-deficient mice; these cells are nontumorigenic as indicated by their failure to form colonies in soft agar and to grow as tumors in immunodeficient SCID mice and in immunocompetent syngeneic hosts. Upon ectopic expression of an activated Ki-ras gene, p53-deficient colon epithelial cells form colonies in soft agar and highly invasive subcutaneous tumors in both immunodeficient and immunocompetent mice. Ectopic expression of wild-type p53, but not of a DNA-binding-deficient mutant, markedly suppressed the colony-forming ability of the Ki-ras-transformed p53-deficient epithelial cells. Together, these findings establish a functional synergism in colorectal tumorigenesis dependent on the effects of an oncogenic Ki-ras in a p53-deficient background. This model of tumorigenic conversion of colon epithelial cells might be useful to identify genetic changes associated with disease progression and to evaluate the therapeutic response to conventional and novel anticancer drugs.


Subject(s)
Colonic Neoplasms/genetics , Genes, p53 , Genes, ras , Animals , Base Sequence , Cell Transformation, Neoplastic/genetics , Colon/metabolism , Colon/pathology , Colonic Neoplasms/etiology , Colonic Neoplasms/pathology , Colorectal Neoplasms/etiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Primers/genetics , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gene Expression Regulation , Humans , Male , Mice , Mice, Knockout , Mice, SCID , Microscopy, Electron , Retroviridae/genetics , Transfection , Tumor Stem Cell Assay
2.
J Physiol Paris ; 87(3): 203-8, 1993.
Article in English | MEDLINE | ID: mdl-8136786

ABSTRACT

We review here evidence that mast cells independently secrete large and small vesicles. Release of small vesicles is triggered by Ca2+. Combining capacitance measurements and flash photolysis of caged Ca2+, we demonstrate Ca-triggered exocytosis that is kinetically identical to the release of dense-core peptidergic vesicles from pituitary melanotrophs. It is suggested that the secretory pathway used for hormone secretion in neuroendocrine cells is also active in mast cells and eosinophils. The nature of the mediator thus secreted is unknown.


Subject(s)
Calcium/physiology , Mast Cells/metabolism , Animals , Kinetics , Melanocyte-Stimulating Hormones/metabolism , Microscopy, Electron , Pituitary Gland/cytology , Pituitary Gland/metabolism , Rats
SELECTION OF CITATIONS
SEARCH DETAIL
...