RGD Reference Report - Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells. - Rat Genome Database

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Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells.

Authors: Glondu, M  Liaudet-Coopman, E  Derocq, D  Platet, N  Rochefort, H  Garcia, M 
Citation: Glondu M, etal., Oncogene 2002 Aug 1;21(33):5127-34.
RGD ID: 1547890
Pubmed: PMID:12140763   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1205657   (Journal Full-text)

Overexpression of cathepsin-D in primary breast cancer has been associated with rapid development of clinical metastasis. To investigate the role of this protease in breast cancer growth and progression to metastasis, we stably transfected a highly metastatic human breast cancer cell line, MDA-MB-231, with a plasmid containing either the full-length cDNA for cathepsin-D or a 535 bp antisense cathepsin-D cDNA fragment. Clones expressing antisense cathepsin-D cDNA that exhibited a 70-80% reduction in cathepsin-D protein, both intra- and extracellularly compared to controls, were selected for further experiments. These antisense-transfected cells displayed a reduced outgrowth rate when embedded in a Matrigel matrix, formed smaller colonies in soft agar and presented a significantly decreased tumor growth and experimental lung metastasis in nude mice compared with controls. However, manipulating the cathepsin-D level in the antisense cells has no effect on their in vitro invasiveness. These studies demonstrate that cathepsin-D enhances anchorage-independent cell proliferation and subsequently facilitates tumorigenesis and metastasis of breast cancer cells. Our overall results provide the first evidence on the essential role of cathepsin-D in breast cancer, and support the development of a new cathepsin-D-targeted therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer  IMP 1547890human gene in a mouse modelRGD 
breast cancer  ISOCTSD (Homo sapiens)1547890; 1547890human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctsd  (cathepsin D)

Genes (Mus musculus)
Ctsd  (cathepsin D)

Genes (Homo sapiens)
CTSD  (cathepsin D)


Additional Information