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1.
Cancer Res ; 61(8): 3472-9, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11309310

ABSTRACT

Mucinous colorectal cancers exhibit a characteristic set of molecular genetic alterations and may be derived from progenitor cells committed to the goblet cell lineage. Previously, we demonstrated that the MUC2 mucin gene promoter drives transgene reporter expression with high specificity in small intestinal goblet cells of transgenic mice. On the basis of these experiments, we reasoned that the MUC2 promoter could be used to drive SV40 T antigen (Tag) expression in the same cell type, decoupling them from their normal antiproliferative controls. A line of mice was established (MUCTag6) that expressed Tag in intestinal goblet cells as determined by RNA blot and immunohistochemical analysis. These goblet cells were markedly involuted however, most notably in the villi. Endogenous intestinal MUC2 message levels were reduced to about one third the normal level in these mice. However, absorptive cell lineage markers were comparable with nontransgenics. Bromodeoxyuridine-positive S-phase cells are limited to crypts in nontransgenic intestine but are present in both crypts and villi in MUCTag6. In contrast, mitotic cells were not present in the villi, indicating that MUCTag6 villi goblet cells do not progress into M phase. Apoptotic cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling were increased more than fourfold in MUCTag6 villi (P < 0.0001), and apoptotic goblet cells were evident. Electron microscopic examination of MUCTag6 intestinal villi revealed the presence of degraded cell remnants containing mucin goblets together with other cell debris, further indicating apoptosis of the goblet cell lineage. Thus, the expression of Tag in intestinal goblet cells releases them from normal antiproliferative controls, causing their inappropriate entry into S phase even after they transverse the crypt/villus junction. They do not, however, progress to M phase. Instead, they undergo apoptosis with a high degree of efficiency in S or G(2) phase. These experiments demonstrate that apoptosis effectively blocks inappropriate goblet cell proliferation in the intestine, supporting its proposed role as an antineoplastic mechanism.


Subject(s)
Antigens, Polyomavirus Transforming/biosynthesis , Apoptosis/physiology , Cell Movement/physiology , Goblet Cells/cytology , Intestine, Small/cytology , Mucins/genetics , Animals , Antigens, Polyomavirus Transforming/genetics , Female , Goblet Cells/immunology , Goblet Cells/metabolism , Intestine, Small/metabolism , Intestine, Small/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Microvilli/physiology , Mucin-2 , Oncogenes , Promoter Regions, Genetic , S Phase/physiology
2.
FEBS Lett ; 482(1-2): 49-53, 2000 Sep 29.
Article in English | MEDLINE | ID: mdl-11018521

ABSTRACT

The dipeptidyl peptidase IV (DPPIV) gene encodes a brush border membrane exopeptidase that is expressed in a tissue-restricted fashion. To examine the regulation of DPPIV transcription in various tissues in vivo, we examined the expression of DPPIV 5'-flanking region (promoter)-human growth hormone reporter constructs in transgenic mice. These mice exhibited cell-type specific reporter expression in kidney. Surprisingly, however, only very low to non-detectable levels of reporter were found in small intestine. These results indicate that DNA elements sufficient for DPPIV expression in kidney, but not intestine, reside in the 5'-flanking region of the gene.


Subject(s)
Dipeptidyl Peptidase 4/genetics , Gene Expression Regulation, Enzymologic , Intestine, Small/enzymology , Kidney/enzymology , Promoter Regions, Genetic , 5' Untranslated Regions/genetics , Animals , Base Sequence , Genes, Reporter , Human Growth Hormone/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Molecular Sequence Data , Organ Specificity , RNA, Messenger/genetics , Transcription, Genetic
3.
Riv Biol ; 82(3-4): 344-5, 416-7, 1989.
Article in English, Italian | MEDLINE | ID: mdl-2483277
4.
J Theor Biol ; 125(4): 419-35, 1987 Apr 21.
Article in English | MEDLINE | ID: mdl-3657220

ABSTRACT

The morphogenesis of the color pattern of animals is modeled within the framework of a clonal model. The model takes into account the, sometimes conflicting, cell-cell and cell-background interactions. The color patterns of some reptiles and mammals are found to be consistent with the predictions of the model.


Subject(s)
Cell Communication , Color , Morphogenesis , Animals , Cats , Lizards , Mice , Models, Biological , Snakes , Thermodynamics
5.
J Theor Biol ; 125(4): 437-47, 1987 Apr 21.
Article in English | MEDLINE | ID: mdl-3657221

ABSTRACT

The morphogenesis of the color pattern of animals is modeled with cellular automata. The cell-cell near neighbor interactions are taken into account and impose restrictions on the model. The allowed patterns are observed in reptiles, felines and fishes.


Subject(s)
Cell Communication , Color , Morphogenesis , Animals , Cats , Cell Differentiation , Clone Cells , Fishes , Models, Biological , Snakes
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