Doxycycline-inducible expression of SPARC/osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition

Dhanesuan, Nirada, Sharp Julie, A., Blick, Tony, Price, John T. and Thompson, Erik W. 2002, Doxycycline-inducible expression of SPARC/osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition, Breast cancer research and treatment, vol. 75, no. 1, pp. 73-85.

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Title Doxycycline-inducible expression of SPARC/osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition
Author(s) Dhanesuan, Nirada
Sharp Julie, A.
Blick, Tony
Price, John T.
Thompson, Erik W.
Journal name Breast cancer research and treatment
Volume number 75
Issue number 1
Start page 73
End page 85
Total pages 13
Publisher Springer New York LLC
Place of publication New York, NY
Publication date 2002
ISSN 0167-6806
1573-7217
Keyword(s) adhesion
doxycycline
proliferation SPARC
Tet-On
Summary SPARC (secreted protein acidic and rich in cysteine)/BM40/Osteonectin is a matricellular protein with multiple effects on cell behaviour. In vitro, its major known functions are anti-adhesive and anti-proliferative, and it is associated with tissue remodelling and cancer in vivo. SPARC is overexpressed in many cancers, including breast cancer, and the effects of SPARC seem to be cell type-specific. To study the effects of SPARC on breast cancer, we transfected SPARC into the MDA-MB-231 BAG, human breast cancer cell line using the Tet-On inducible system. By western analysis, we found low background levels in the MDA-MB-231 BAG and clone X parental cells, and prominent induction of SPARC protein expression after doxycycline treatment in SPARC transfected clones X5, X21, X24 and X75. Induction of SPARC expression did not affect cell morphology or adhesiveness to collagens type I and IV, but it slowed the rate of proliferation in adherent cultures. Cell cycle analysis showed that SPARC slowed the progression to S phase. Doxycycline induction of SPARC also slowed the rate of monolayer wound closure in the cultured wound healing assay. Thymidine inhibition of proliferation abrogated this effect, confirming that it was due to anti-proliferation rather than inhibition of migration. Consistent with this, we were unable to detect any differences in migration and Matrigel outgrowth analysis of doxycycline-stimulated cells. We conclude that SPARC is inhibitory to human breast cancer cell proliferation, and does not stimulate migration, in contrast to its stimulatory effects reported for melanoma (proliferation and migration) and glioma (migration) cells. Similar growth repression by SPARC has been reported for ovarian cancer cells, and this may be a common feature among carcinoma.
Language eng
Field of Research 111201 Cancer Cell Biology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2002, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30061501

Document type: Journal Article
Collections: School of Medicine
School of Life and Environmental Sciences
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