Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells Journal Article
| Authors: | Arber, N.; Doki, Y.; Han, E. K. H.; Sgambato, A.; Zhou, P.; Kim, N. H.; Delohery, T.; Klein, M. G.; Holt, P. R.; Weinstein, I. B. |
| Article Title: | Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells |
| Abstract: | Cyclin D1 plays an important role in regulating the progression of cells through the G1 phase of the cell cycle. This gene is frequently overexpressed in human colon cancer. To address the role of cyclin D1 in growth control and tumorigenesis in this disease, we have overexpressed an antisense eyelin D1 cDNA construct in the human colon cancer cell line SW48OE8, which expresses high levels of cyclin D1. The integration and expression of the antisense construct was verified by Southern and Northern blot analyses, respectively, and resulted in decreased expression of the cyclin D1 protein. This was associated with decreased levels of the Rb and p27(Kipl) proteins. In addition, the hypophosphorylated form of Rb was increased in these cells. The SW480E8 antisense cyclin D1 cells displayed an increased doubling time, a decrease in saturation density, decreased plating efficiency and anchorage- independent growth, and a loss of tumorigenicity in nude mice. These findings provide direct evidence that increased expression of cyclin D1 in colon tumor cells contributes to their abnormal growth and tumorigenicity. The ability to revert the transformed phenotype of these cells with antisense cyclin D1 suggests that cyclin D1 or its associated cyclin-dependent kinase 4 may be useful targets in the therapy of colon cancer. |
| Keywords: | controlled study; human cell; proto-oncogene proteins; drug targeting; animals; cell cycle proteins; mice; cell cycle; cell division; gene overexpression; cancer prevention; neoplasm proteins; tumor markers, biological; colonic neoplasms; dna, antisense; down-regulation; tumor cells, cultured; cancer therapy; genetic vectors; cancer inhibition; mice, nude; protein-serine-threonine kinases; colon cancer; oncogene proteins; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; cyclin d1; cyclin-dependent kinases; cyclins; cyclin dependent kinase; retinoblastoma protein; anchorage independent growth; phosphoprotein; complementary dna; colon carcinogenesis; cyclin-dependent kinase 4; cyclin-dependent kinase 6; microtubule-associated proteins; humans; human; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 57 |
| Issue: | 8 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1997-04-01 |
| Start Page: | 1569 |
| End Page: | 1574 |
| Language: | English |
| PUBMED: | 9108461 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
