+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Diminished G1 checkpoint after gamma-irradiation and altered cell cycle regulation by insulin-like growth factor II overexpression

, : Diminished G1 checkpoint after gamma-irradiation and altered cell cycle regulation by insulin-like growth factor II overexpression. Journal of Biological Chemistry 274(19): 13118-13126

High levels of insulin-like growth factor II (IGFII) mRNA expression are detected in many human tumors of different origins including rhabdomyosarcoma, a tumor of skeletal muscle origin. To investigate the role of IGFII in tumorigenesis, we have compared the mouse myoblast cell line C2C12-2.7, which was stably transfected with human IGFII cDNA and expressed high and constant amounts of IGFII, to a control cell line C2C12-1.1. A rhabdomyosarcoma cell line, RH30, which expresses high levels of IGFII and contains mutated p53, was also used in these studies. IGFII overexpression in mouse myoblast C2C12 cells causes a reduced cycling time and higher growth rate. After gamma-irradiation treatment, C2C12-1.1 cells were arrested mainly in G0/G1 phase. However, C2C12-2.7 and RH30 cells went through a very short G1 phase and then were arrested in an extended G2/M phase. To verify further the effect of IG-FII on the cell cycle, we developed a Chinese hamster ovary (CHO) cell line with tetracycline-controlled IGFII expression. We found that CHO cells with high expression of IGFII have a shortened cycling time and a diminished G1 checkpoint after treatment with methylmethane sulfonate (MMS), a DNA base-damaging agent, when compared with CHO cells with very low IGFII expression. It was also found that IGFII overexpression in C2C12 cells was associated with increases in cyclin D1, p21, and p53 protein levels, as well as mitogen-activated protein kinase activity. These studies suggest that IGFII overexpression shortens cell cycling time and diminishes the G1 checkpoint after DNA damage despite an intact p53/p21 induction. In addition, IGFII overexpression is also associated with multiple changes in the levels and activities of cell cycle regulatory components following gamma-irradiation. Taken together, these changes may contribute to the high growth rate and genetic alterations that occur during tumorigenesis.


PMID: 10224065

Other references

Gutenberg, B., 1950: Structure of the earth's crust in the continents. Science 111(2872): 29-29

Nee, P.F.; Joiner, K.A., 2000: Toxoplasmosis. The management of toxoplasmosis (Toxoplasma gondii) is reviewed with reference to life cycle and epidemiology, clinical spectrum and diagnosis, drug therapy, and disease prevention with particular reference to AIDS. Pyrimethamine and sulfadiazine...

Begley, S., 2001: IV. Genes, cells, drugs. Cures for the future. New DNA in old bodies. Newsweek 138(11a): 82-83

Rosenkrantz, A.B.; Mussi, T.C.; Somberg, M.B.; Taneja, S.S.; Babb, J.S., 2012: Comparison of CT-based methodologies for detection of growth of solid renal masses on active surveillance. The purpose of this study is to retrospectively compare 1D, 2D, and 3D measurements on CT for detection of growth of solid renal masses on active surveillance. Forty solid renal masses measuring at least 1 cm in patients who underwent two CT studi...

Koenig J.L., 1969: Raman spectroscopy of poly l proline in aqueous solution. Biopolymers: 173-179

Allen, W.A.; Rajotte, E.G., 1990: The changing role of extension entomology in the IPM era. Integrated pest management (IPM) programmes have had a remarkable influence on extension entomology over the past 20 years. In this review, a brief history of extension entomology is given, followed by a detailed discussion on IPM and extension en...

Abdullaeva T.M., 1973: Effect of growth regulators on content of carbohydrates in rooted leaf grafts. Fiziologiya i Biokhimiya Kul'turnykh Rastenii 5(4): 431-436

Olsen, E.A.; Bergfeld, W.; Cotsarelis, G.; Price, V.; Shapiro, J.; Sinclair, R.; Solomon, A.; Sperling, L.; Stenn, K.; Whiting, D.; The Cicatricial Alopecia Research Group, 2003: Cicatricial alopecia Consensus conference guidelines. Journal of Investigative Dermatology Symposium Proceedings 8(1): 130, June

Thies J.E.; Bohlool B.B.; Singleton P.W., 1989: Barriers to performance of introduced rhizobia importance of indigenous populations. Abstracts of the Annual Meeting of the American Society for Microbiology 89: 300

Yen, J-Yu.; Ko, C-Hung.; Yen, C-Fang.; Yang, M-Jen.; Wu, C-Yuh.; Juan, C-Hui.; Hou, M-Feng., 2006: Quality of life, depression, and stress in breast cancer women outpatients receiving active therapy in Taiwan. The aims of the present study were to compare the quality of life (QoL), depression and stress between patients with malignant breast cancer and those with benign breast tumors. The present study also examined the factors related to QoL among the...