TY - JOUR
T1 - Oncogenic transformation of normal enterocytes by overexpression of cyclin D1
AU - Kazanov, Diana
AU - Shapira, Itzhak
AU - Pick, Marjorie
AU - Kolker, Olga
AU - Liberman, Eliezer
AU - Deutsch, Varda
AU - Strier, Loudmilla
AU - Dvory-Sobol, Hadas
AU - Kunik, Talya
AU - Arber, Nadir
N1 - Funding Information:
Funding from the Israel Cancer Association (to N.A.), and the Shapira foundation (to D.K.) supported this study.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cyclin D1
KW - Enterocytes
KW - Tumorigenicity
KW - β-catenin
UR - http://www.scopus.com/inward/record.url?scp=0037712150&partnerID=8YFLogxK
U2 - 10.1023/A:1024138605802
DO - 10.1023/A:1024138605802
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C2 - 12870780
AN - SCOPUS:0037712150
VL - 48
SP - 1251
EP - 1261
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
SN - 0163-2116
IS - 7
ER -