Regulation of protein degradation in normal and transformed human bronchial epithelial cells in culture

Lee, Hsiang-Kuang; Jones, Raymond T.; Myers, Roy A.M.; Marzella, Louis

doi:10.1016/0003-9861(92)90572-e

Cited by 21 publications

(8 citation statements)

References 30 publications

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“…For example, protein degradation rates in transformed fibroblasts were lower than their nontransformed counterparts, especially under nutrient and/or serum starvation conditions (Gunn et al, 1977;Lockwood and Minassian, 1982;Cockle and Dean, 1984;Gronostajski and Pardee, 1984;Knecht et al, 1984). This fitted the more general observations that the rate of cell growth is influenced by a balance between the rates of protein synthesis and autophagic degradation of long-lived proteins, the latter being significantly lower in proliferating cells than in stationary cells (Hendil, 1977;Otsuka and Moskowitz, 1978;Pfeifer and Dunker, 1985;Papadopoulos and Pfeifer, 1987;Pfeifer et al, 1988;Tessitore et al, 1988;Lee et al, 1992).…”

Section: Autophagic Capacity and Cellular Transformationmentioning

confidence: 69%

Autophagy as a cell death and tumor suppressor mechanism

2004

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Autophagy is characterized by sequestration of bulk cytoplasm and organelles in double or multimembrane autophagic vesicles, and their delivery to and subsequent degradation by the cell's own lysosomal system. Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Increasing lines of evidence indicate that these molecular mechanisms may be recruited by an alternative, caspase-independent form of programmed cell death, named autophagic type II cell death. In some settings, autophagy and apoptosis seem to be interconnected positively or negatively, introducing the concept of 'molecular switches' between them. Additionally, mitochondria may be central organelles integrating the two types of cell death. Malignant transformation is frequently associated with suppression of autophagy. The recent implication of tumor suppressors like Beclin 1, DAP-kinase and PTEN in autophagic pathways indicates a causative role for autophagy deficiencies in cancer formation. Autophagic cell death induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality.

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Section: Autophagic Capacity and Cellular Transformationmentioning

confidence: 69%

Autophagy as a cell death and tumor suppressor mechanism

2004

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“…In an experimental pancreas cancer model, increased autophagy was observed in the step of the tumor formation (14). Starvation-induced protein degradation was not down-regulated among transformed and transformed-tumorigenic bronchial epithelial cells compared with their normal counterparts (15). A high potential of autophagic protein degradation was observed in an undifferentiated colon cancer cell line HT29 (16).…”

Section: Discussionmentioning

confidence: 82%

Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation

Tsuchihara²,

et al. 2007

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Several types of cancer cells, including colorectal cancerderived cell lines, show austerity, the resistance to nutrient starvation, but exactly how cancer cells obtain energy sources under conditions in which their external nutrient supply is extremely limited remains to be clarified. Because autophagy is a catabolic process by which cells supply amino acids from self-digested organelles, cancer cells are likely to use autophagy to obtain amino acids as alternative energy sources. Amino acid deprivation-induced autophagy was assessed in DLD-1 and other colorectal cancer-derived cell lines. The autophagosome-incorporated LC3-II protein level increased after treatment with a combination of autolysosome inhibitors, which interferes with the consumption of autophagosomes. Autophagosome formation was also morphologically confirmed using ectopically expressed green fluorescent protein-LC3 fusion proteins in DLD-1 and SW480 cells. These data suggest that autophagosomes were actively produced and promptly consumed in colorectal cancer cells under nutrient starvation. Autolysosome inhibitors and 3-methyl adenine, which suppresses autophagosome formation, remarkably enhanced apoptosis under amino acid-deprived and glucosedeprived condition. Similar results were obtained in the cells with decreased ATG7 level by the RNA interference. These data suggest that autophagy is pivotal for the survival of colorectal cancer cells that have acquired austerity. Furthermore, autophagosome formation was seen only in the tumor cells but not in the adjacent noncancerous epithelial cells of colorectal cancer specimens. Taken together, autophagy is activated in colorectal cancers in vitro and in vivo, and autophagy may contribute to the survival of the cancer cells in their microenvironment. [Cancer Res 2007;67(20):9677-84]

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“…In ras transfected cells, a decrease in the most abundant aspartic endopeptidase, Cat D, and relative increases of cysteine cathepsins were observed: Lee et al [38] reported that basal protein degradation was lowered by 27% after viral c-Ha-ras oncogene transformation in human bronchial epithelial cells. The down-regulation of autophagic protein degradation after ras transfection, observed also in other cell types, may be part of the mechanism controlling the cellular protein turnover [39].…”

Section: Discussionmentioning

confidence: 99%

Cathepsins D, B, and L in transformed human breast epithelial cells

Lah

Calaf

Kálmán

et al. 1996

Breast Cancer Res Tr

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To investigate the regulation of lysosomal enzymes during carcinogenesis, we measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast epithelial cell line, and cells evolved after treatment with carcinogen and transfected with c-Ha-ras oncogene. The clones used in this study, MCF-10FTras, D3, D3-1, and D3-1Tras, expressed no estrogen receptors and gradually increased invasive potential, while oncogene-transfected lines were also tumorigenic in SCID mice [16, 19]. Cats D, B, and L were determined in the cells and in cell media using enzyme-linked immunosorbent assay (ELISA), specific enzyme activity measurements, and immunocytochemistry. The major intra- and extracellular lysosomal proteinase in these cells was Cat D (30-180 pm/mg), followed by Cat B (2-10 pm/mg) and Cat L (1-5 pm/mg). An inverse relationship between intracellular Cat D levels and invasive potential of carcinogen-treated and c-Ha-ras oncogene-transfected cell lines was observed. No significant changes in extracellular concentration of Cat D precursor in this series of cell lines was observed. Intracellular levels of Cats B and L were unchanged or slightly lower in carcinogen-treated D3 and D3-1 cells, as well as in MCF-10FTras. On the other hand, in D3-1Tras cell line, evolving from c-Ha-ras transfected D3-1 line, 3.5 fold and 4.4 fold increases in Cat B and Cat L, respectively, but a 2 fold decrease in Cat D, were observed compared to the parental cell line. Immunocytochemical staining showed a granular, polarized perinuclear and cytoplasmic staining of cathepsins in all cell lines. Cysteine proteinases stained more frequently and more intensely in D3-1Tras compared to other lines, confirming the immunochemical assays. We hypothesize that several molecular events, caused by a carcinogen and an oncogene such as c-Ha-ras, are needed to increase Cat B and Cat L, but not Cat D, expression. Therefore, the cysteine and aspartic lysosomal proteinases are differentially expressed in the breast cell lines with more invasive phenotype.

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Regulation of protein degradation in normal and transformed human bronchial epithelial cells in culture

Cited by 21 publications

References 30 publications

Autophagy as a cell death and tumor suppressor mechanism

Autophagy as a cell death and tumor suppressor mechanism

Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation

Cathepsins D, B, and L in transformed human breast epithelial cells

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