Association of deficient DNA repair during G2 phase with progression from benign to malignant state in a line of human skin keratinocytes transfected with ras oncogene.
Human skin keratinocytes after malignant neoplastic transformation by infection with Kirsten murine sarcoma virus (KiMSV) or transfection with pSV2 ras (containing an activated c-Ha-ras oncogene) showed a DNA repair deficiency(ies). The repair deficiency was manifest as an abnormally high frequency of chromatid breaks and gaps persisting after X-ray-induced DNA damage inflicted during the G2 phase of the cell cycle. Non-tumorigenic control cells at that time were clearly repair-efficient. By analyzing benign and malignant tumorigenic HaCaT-ras clones, we could exclude ras p21 oncoprotein expression as the causal mechanism for repair deficiency, since both clone types expressed similar levels of the mutated protein and only the malignant tumorigenic cells showed repair deficiency. The results suggest that mutated p21 ras provided the human keratinocytes with a growth advantage in vivo (benign tumor growth), but acquisition of repair deficiency is required for progression from benign to malignant state.
Parshad
R
R
Department of Pathology, College of Medicine, Howard University, Washington, DC.
Sanford
K K
KK
Price
F M
FM
Rhim
J S
JS
Tarone
R E
RE
Fusenig
N E
NE
Boukamp
P
P
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002842:Chromatids / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D016195:G2 Phase / Q000502:physiology* / Q000528:radiation effects; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D011905:Genes, ras / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D012879:Skin Physiological Phenomena; D014162:Transfection
D004273:DNA, Neoplasm