Oncogenic transformation of normal enterocytes by overexpression of cyclin D1

Diana Kazanov, Itzhak Shapira, Marjorie Pick, Olga Kolker, Eliezer Liberman, Varda Deutsch, Loudmilla Strier, Hadas Dvory-Sobol, Talya Kunik, Nadir Arber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesize that normal enterocytes over-expressing cyclin D1 will demonstrate a transformed phenotype. The nontumorigenic intestinal epithelial cell line, IEC-18, was transfected with the vector pMV7-CCND1, encoding cyclin D1. Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further evaluated in comparison to the vector control cells. They proliferated faster and demonstrated anchorage-independent growth in soft agar, higher saturation density, and higher plating efficiency. When injected into nude mice, tumors were generated after 6-8 weeks. On the other hand these cells were more sensitive to induction of apoptosis. There was no change in the level of β-catenin protein. In conclusion, cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal epithelial cells. This model may be useful for understanding the role and interrelationships of cyclin D1 in colorectal tumorigenesis.

Original languageEnglish
Pages (from-to)1251-1261
Number of pages11
JournalDigestive Diseases and Sciences
Issue number7
StatePublished - 1 Jul 2003


  • Apoptosis
  • Cyclin D1
  • Enterocytes
  • Tumorigenicity
  • β-catenin


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