title: Phospholipase D prevents apoptosis in v-Src-transformed rat fibroblasts and MDA-MB-231 breast cancer cells.
abstract: Phospholipase D (PLD) activity is elevated in response to mitogenic and oncogenic signals. PLD also cooperates with overexpressed tyrosine kinases to transform rat fibroblasts. 3Y1 rat fibroblasts overexpressing the tyrosine kinase c-Src undergo apoptosis in response to serum withdrawal. We report here that elevated expression of either PLD1 or PLD2 in these cells prevents apoptosis induced by serum withdrawal. 3Y1 cells transformed by the activated tyrosine kinase v-Src have elevated PLD activity and are resistant to apoptosis induced by serum withdrawal. However, if PLD activity is blocked, the v-Src-transformed cells underwent apoptosis. MDA-MB-231 cells are a human breast cancer cell line with substantially elevated levels of PLD activity. Inhibiting PLD activity in these cells similarly rendered them sensitive to the apoptotic insult of serum withdrawal. These data indicate that elevated PLD activity generates a survival signal(s) allowing cells to overcome default apoptosis programs.
authors.affiliation: Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10021, USA.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhong
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Troy
authors.initials: T
authors.lastname: Joseph
authors.forename: Desmond
authors.initials: D
authors.lastname: Jackson
authors.forename: David A
authors.initials: DA
authors.lastname: Foster
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D015688:Oncogene Protein pp60(v-src); D010739:Phospholipase D