title: Effect of constitutively active Ras overexpression on cell growth in recombinant Chinese hamster ovary cells.
abstract: Constitutively active Ras (CA-Ras) is known to enhance cell growth through the induction of various signaling cascades including the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/ERK signaling pathways, although the cellular response is highly dependent on the cell type. To evaluate the effect of CA-Ras overexpression on cell growth in recombinant Chinese hamster ovary (rCHO) cells, an erythropoietin (EPO)-producing rCHO cell line with regulated CA-Ras overexpression (EPO-off-CA-Ras) was established using the Tet-off system. The CA-Ras expression level in EPO-off-CA-Ras cells was tightly regulated by doxycycline addition. Although CA-Ras overexpression slightly increased the viable cell concentration during the late exponential phase, it did not increase the maximum viable cell concentration or specific growth rate to a significant degree. Unexpectedly, CA-Ras overexpression in rCHO cells led only to the enhancement in the activation of the MAPK/ERK signaling pathway and not the PI3K/Akt signaling pathway. Taken together, CA-Ras overexpression in rCHO cells did not significantly affect cell growth; it also had no critical impact on viable cell concentration or EPO production, possibly due to a failure to activate the PI3K/Akt signaling pathway.
authors: Department of Biological Sciences, Graduate School of Nanoscience and Technology (WCU), KAIST, Daejon 305-701, Korea.
authors: Yeon-Gu
authors: YG
authors: Kim
authors: Young Kue
authors: YK
authors: Han
authors: Jee Yon
authors: JY
authors: Kim
authors: Eun Gyo
authors: EG
authors: Lee
authors: Hong Weon
authors: HW
authors: Lee
authors: Gyun Min
authors: GM
authors: Lee
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004318:Doxycycline / Q000494:pharmacology; D004921:Erythropoietin; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics* / Q000494:pharmacology*
chemical_list: D004921:Erythropoietin; D018631:ras Proteins; D004318:Doxycycline