Establishment of a colonic adenoma cell line (GEKI-2): spectral karyotype analysis and functional characterization.
OBJECTIVE
On the genetic level colonic carcinogenesis is best described by the adenoma-carcinoma sequence, but it may be modulated by exogenous factors, particularly by dietary factors and chemopreventive agents. The protective effects of exogenous factors are thought to be exerted rather in the early stages of the adenoma-carcinoma sequence. Thus, an in vitro model consisting of cells stemming from an colon adenoma would be desirable. However, establishing such a cell line has proven difficult.


METHODS
We report the establishment of a colon adenoma cell line. The cells were generated from a colon adenoma and propagated as a stable cell line for more than 40 passages. The cells are microsatellite stable and confirmed to be of epithelial origin by cytokeratin staining.


RESULTS
In contrast to commercially available colon cancer cell lines, cytogenetic analysis with spectral karyotype analysis revealed no chromosomal alterations in this adenoma cell line. Incubation with butyrate resulted in a time- and dose-dependent inhibition of proliferation and in an significant increase in cellular differentiation. The cdk inhibitor p21/waf which plays a pivotal role in growth inhibition and differentiation is expressed consecutively in GEKI-2 cells. The expression of cdk1 and cdk2, important regulatory elements in the cell cycle, is downregulated following treatment with butyrate.


CONCLUSIONS
The presented colon adenoma cell line GEKI-2 may prove a versatile tool for further exploring the underlying mechanisms of protective and promoting factors in early colon cancerogenesis.
Menzel
Thomas
T
Division of Gastroenterology, Department of Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany. menzel_t@medizin.uni-wuerzburg.de
Melcher
Ralph
R
Koehler
Sigrid
S
Dusel
Gerda
G
Backhaus
Kerstin
K
Ott
German
G
Breithaupt
Wolfram
W
Al-Taie
Oliver
O
Schauber
Jürgen
J
Gostner
Andrea
A
Scheppach
Wolfgang
W
Lührs
Hardi
H
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D032681:Spectral Karyotyping
D002087:Butyrates; D002272:Carcinoembryonic Antigen