Online citations, reference lists, and bibliographies.
← Back to Search

Cathepsins D, B, And L In Transformed Human Breast Epithelial Cells

Tamara T. Lah, G. Calaf, E. Kálmán, B. G. Shinde, R. Somers, S. Estrada, E. Salero, J. Russo, I. Daskal
Published 2005 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
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 oncogenetransfected 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 carcinogentreated 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.
This paper references
The role of cathepsin L in malignant transformation.
S. Kane (1990)
Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting.
C. Gabel (1983)
Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency.
M. Garcia (1990)
Developmental expression of cathepsin L and c‐rasHa in the mouse placenta
R. T. Hamilton (1991)
Stefins and cathepsins in breast carcinoma
TT Lah (1992)
A protease involved in breast cancer metastasis.
H. Rochefort (1990)
Regulation of protein degradation in normal and transformed human bronchial epithelial cells in culture.
H. K. Lee (1992)
Breast Susceptibility to Carcinogenesis
J. Russo (1996)
Biological and molecular bases of mammary carcinogenesis.
J. Russo (1987)
Stefins and lysosomal cathepsins B, L and D in human breast carcinoma
T. Lah (1992)
Ras-responsive genes and tumor metastasis.
A. Chambers (1993)
11 Alterations in Processing and Trafficking of Cathepsin B during Malignant Progression
Bonnie F. Sloane (1994)
Cathepsin D: A protease involved in breast cancer metastasis
H. Rochefort (2004)
Lysosomal enzymes and their endogenous inhibitors in neoplasia
K Sloane BE Moin (1993)
Cathepsins B and L , but not cathepsin D , are related to the progression of human breast epithelial cells ( HBEC ) transformation abstract ~ a ° I
T Lah (1994)
Lysosomal proteinases in malignant breast carcinoma
I Vrhovec (1992)
Human liver cathepsin L.
R. Mason (1985)
Expression of cathepsin L in human tumors.
S. Chauhan (1991)
Estradiol increases the secretion by MCF7 cells of several lysosomal pro-enzymes.
F. Capony (1990)
Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10.
Herbert D. Soule (1990)
Evaluation of cathepsin D as a prognostic factor in breast cancer
P. Ravdin (1993)
The identification of active forms of cysteine proteinases in Kirsten-virus-transformed mouse fibroblasts by use of a specific radiolabelled inhibitor.
R. Mason (1989)
Protein turnover in 3T3 cells transformed with the oncogene c-H-ras1.
J. Gunn (1992)
Daskal I: Cathepsins B and L, but not cathepsin D, are related to the progression of human breast epithelial cells (HBEC) transformation abstract ~a°I
T Lah (1994)
cHa-ras oncogene enhances the tumorigenic phenotype of human breast epithelial cells transformed with a chemical carcinogen in vitro
G Calaf (1993)
The identification of the major excreted protein (MEP) from a transformed mouse fibroblast cell line as a catalytically active precursor form of cathepsin L.
R. Mason (1987)
Interrelationship of active and latent secreted human cathepsin B precursors.
J. Mort (1986)
Membrane association of cathepsin B can be induced by transfection of human breast epithelial cells with c-Ha-ras oncogene.
Bonnie F. Sloane (1994)
Lysosomal proteinases in malignant breast carcinoma
I Vrhovec (1992)
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
M. M. Bradford (1976)
Cathepsins D, B and L in breast carcinoma and in transformed human breast epithelial cells (HBEC).
T. Lah (1995)
Increased expression of cathepsins L and B and decreased activity of their inhibitors in metastatic, ras‐transformed NIH 3T3 cells
A. Chambers (1992)
Transformation of human breast epithelial cells by chemical carcinogens.
G. Calaf (1993)
Demonstration of proteinase inhibitors cystatin A, B and C in breast cancer and in cell lines MCF-7 and ZR-75-1.
Z. Kolář (1989)
Biological Functions of Proteases and Inhibitors
N. Katunuma (1994)
In vitro degradation of extracellular matrix by human ovarian carcinoma cells
M. J. Niedbala (2004)
Transformation of Human Breast Epithelial Cells by c‐Ha‐ras Oncogene
F. Basolo (1991)
The major excreted protein of transformed fibroblasts is an activable acid-protease.
S. Gal (1986)
Cathepsins B, H and L in human breast carcinoma.
D. Gabrijelčič (1992)
The role of cathepsin D in the invasiveness of human breast cancer cells.
M. Johnson (1993)
Cysteine endopeptidases and their inhibitors in malignant progression of rat embryo fibroblasts.
Bonnie F. Sloane (1992)
The identification of active forms of cysteine proteinases in Kirsten-virus transformed mouse fibroblasts by use of a specific radiolabelled inhibitor
RW Mason (1989)
Immunoradiometric assay of pro-cathepsin D in breast cancer cytosol: relative prognostic value versus total cathepsin D.
J. Brouillet (1993)
A rapid, sensitive method for the quantitation of gg quantities of protein, utilizing the principle of proteindye binding
M Bradford (1976)
Lysosomal enzymes and their endogenous inhibitors in neoplasia
K Sloane BE Moin (1993)
Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection
G. Calaf (2004)
Allele loss and point mutation in codons 12 and 61 of the c‐Ha‐ras oncogene in carcinogen‐transformed human breast epithelial cells
P. L. Zhang (1994)
Cytochemical and biochemical evidence of cathepsin B in malignant, transformed and normal breast epithelial cells.
E. Křepela (1987)
Fibroblasts transformed by different ras oncogenes show dissimilar patterns of protease gene expression and regulation.
J. Zhang (1992)
Cathepsins B and L , but not cathepsin D , are related to the progression of human breast epithelial cells ( HBEC ) transformation abstract ~ a ° I
T Lah (1994)
The role of cathepsin L in malignant transformation.
Kane Se (1990)

This paper is referenced by
Lysosomal Enzymes, Cathepsins in Brain Tumour Invasion
N. Levičar (2004)
Expression of cathepsin B is related to tumorigenicity of breast cancer cell lines
I. Zajc (2003)
Inhibition of Cathepsin D protease activity by Punica granatum fruit peel extracts, isolates, and semisynthetic analogs
A. K. Chaturvedi (2012)
Proteomic analysis of global alteration of protein expression in squamous cell carcinoma of the esophagus
G. Zhou (2005)
Role of somatic cells on dairy processes and products: a review
N. Li (2014)
Invasiveness of Transformed Human Breast Epithelial Cell Lines Is Related to Cathepsin B and Inhibited by Cysteine Proteinase Inhibitors
A. Bervar (2003)
Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.
V. Srivastava (2006)
Somatic Cells in Relation to Udder Health and Milk Quality-A Review
T. Malik (2018)
Cathepsin L targeting in cancer treatment.
Dhivya R. Sudhan (2015)
Breast and Colorectal Carcinomas Cathepsin L 2 , a Novel Human Cysteine Proteinase Produced by Updated
Ifligo Santamarla (2006)
The relationship between milk somatic cell count and cheese production, quality and safety: A review
M. Moradi (2021)
Synthesis, antioxidant and cathepsin D inhibition activity of quaternary ammonium chitosan derivatives.
W. Li (2016)
The expression of lysosomal proteinases and their inhibitors in breast cancer: Possible relationship to prognosis of the disease
T. Lah (2008)
Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk sea Fucus evanescens brown alga
T. V. Alekseyenko (2007)
Xenograft Models of Premalignant Breast Disease
F. Miller (2004)
Semantic Scholar Logo Some data provided by SemanticScholar