RGD Reference Report - Malignant transformation of normal enterocytes following downregulation of Bak expression. - Rat Genome Database

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Malignant transformation of normal enterocytes following downregulation of Bak expression.

Authors: Liberman, E  Naumov, I  Kazanov, D  Dvory-Sobol, H  Sagiv, E  Birkenfeld, S  Deutsch, V  Trakhtenbrot, L  Moshkowitz, M  Arber, N 
Citation: Liberman E, etal., Digestion. 2008;77(1):48-56. Epub 2008 Mar 18.
RGD ID: 2316126
Pubmed: PMID:18349538   (View Abstract at PubMed)
DOI: DOI:10.1159/000121411   (Journal Full-text)

Bak is a pro-apoptotic gene, which plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesized that downregulation of Bak expression in normal enterocytes will result in a transformed phenotype. The nontumorigenic intestinal epithelial cell line (IEC18) was transfected with the vector pMV12-AS-bak (encoding anti-sense bak). Three clones, with Bak protein levels similar to those seen in colon cancer cell lines and significantly lower than those found in the parental cells, were further evaluated. The three clones proliferated faster, demonstrated anchorage-independent growth in soft agar and a higher saturation density and plating efficiency. Furthermore, when injected into nude mice, these cells generated tumors after approximately 2-3 weeks. The cells were more resistant to the induction of apoptosis by sulindac sulfide and sulindac sulfone but more sensitive to COX 2 inhibitors (celecoxib and nimesulide). The levels of p16, cyclin D1 and COX 2 were higher in the three transformed clones. In summary,downregulation of Bak expression in normal enterocytes contributes to abnormal growth and tumorigenesis. COX 2 inhibitors may serve as important agents in the prevention and treatment of CRC as they only inhibit the growth of malignant cells.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of cell population proliferation  IMP 2316126 RGD 
negative regulation of gene expression  IMP 2316126p16 more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bak1  (BCL2-antagonist/killer 1)


Additional Information