Oncogenic transformation of normal enterocytes by overexpression of cyclin D1.
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 beta-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.
Kazanov
Diana
D
Gastrointestinal Oncology Unit, Tel Aviv Medical Center and Tel Aviv University, Tel Aviv, Israel.
Shapira
Itzhak
I
Pick
Marjorie
M
Kolker
Olga
O
Liberman
Eliezer
E
Deutsch
Varda
V
Strier
Loudmilla
L
Dvory-Sobol
Hadas
H
Kunik
Talya
T
Arber
Nadir
N
D000818:Animals; D017209:Apoptosis; D018929:Cell Culture Techniques; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D018076:DNA, Complementary; D020895:Enterocytes / Q000378:metabolism* / Q000473:pathology*; D005822:Genetic Vectors; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D015534:Trans-Activators / Q000096:biosynthesis; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1