Biomaterial Database

Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia. 1996

K Polyak, and S R Hamilton, and B Vogelstein, and K W Kinzler

Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Aberrant crypt foci with dysplasia are thought to be the first detectable lesions of colorectal neoplasia. Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21 WAF1/CIP1 and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis. In colorectal epithelium, p21 WAF1/CIP1 expression was undetectable in the lower third of the crypts, where Ki67 was expressed, but then sharply increased as cells passed out of the proliferating zone and migrated toward the humen. Hyperplastic polyps retained this normal compartmentalized pattern. In contrast, markedly decreased p21 WAF1/CIP1 immunostaining was observed in dysplastic aberrant crypt foci as well as in small adenomas. Moreover, the compartmentalization of Ki67 and p21 WAF1/CIP1 was lost, as Ki67 expression extended into the small p21-expressing zone at the top of the crypts. These data suggest that the dysregulated expression of cell-cycle-controlling genes and the consequent release from normal cell cycle controls may represent an essential early step in colorectal neoplasia.

UI	MeSH Term	Description	Entries
D006965	Hyperplasia	An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.	Hyperplasias
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009363	Neoplasm Proteins	Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.	Proteins, Neoplasm
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011125	Adenomatous Polyposis Coli	A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.	Polyposis Coli, Familial,Polyposis Syndrome, Familial,Adenomatous Polyposis Coli, Familial,Adenomatous Polyposis of the Colon,Familial Adenomatous Polyposis,Familial Adenomatous Polyposis Coli,Familial Adenomatous Polyposis of the Colon,Familial Intestinal Polyposis,Familial Multiple Polyposi,Familial Multiple Polyposis,Familial Multiple Polyposis Syndrome,Familial Polyposis Coli,Familial Polyposis Syndrome,Familial Polyposis of the Colon,Hereditary Polyposis Coli,Myh-Associated Polyposis,Polyposis Coli,Polyposis, Adenomatous Intestinal,Adenomatous Intestinal Polyposes,Adenomatous Intestinal Polyposis,Adenomatous Polyposes, Familial,Adenomatous Polyposis Colus,Adenomatous Polyposis, Familial,Coli, Adenomatous Polyposis,Coli, Familial Polyposis,Coli, Hereditary Polyposis,Coli, Polyposis,Colus, Adenomatous Polyposis,Colus, Familial Polyposis,Colus, Hereditary Polyposis,Colus, Polyposis,Familial Adenomatous Polyposes,Familial Intestinal Polyposes,Familial Multiple Polyposes,Familial Multiple Polyposus,Familial Polyposis Colus,Familial Polyposis Syndromes,Hereditary Polyposis Colus,Intestinal Polyposes, Familial,Intestinal Polyposis, Adenomatous,Intestinal Polyposis, Familial,Multiple Polyposes, Familial,Multiple Polyposi, Familial,Multiple Polyposis, Familial,Multiple Polyposus, Familial,Myh Associated Polyposis,Myh-Associated Polyposes,Polyposes, Familial Adenomatous,Polyposes, Familial Multiple,Polyposes, Myh-Associated,Polyposi, Familial Multiple,Polyposis Coli, Adenomatous,Polyposis Coli, Hereditary,Polyposis Colus,Polyposis Colus, Adenomatous,Polyposis Colus, Familial,Polyposis Colus, Hereditary,Polyposis, Familial Adenomatous,Polyposis, Familial Multiple,Polyposis, Myh-Associated,Polyposus, Familial Multiple
D002453	Cell Cycle	The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.	Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D003111	Colonic Polyps	Discrete tissue masses that protrude into the lumen of the COLON. These POLYPS are connected to the wall of the colon either by a stalk, pedunculus, or by a broad base.	Colonic Polyp,Polyp, Colonic,Polyps, Colonic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults