The Journal of Experimental Medicine
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Published online 8 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1675/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 10, May 15, 2000 1675-1686

Original Article

Suppression of Tumorigenicity in Breast Cancer Cells by the Microfilament Protein Profilin 1

Jürgen Jankea, Kathrin Schlüterb, Burkhard Jandriga, Michael Theilea, Konrad Kölblec,e, Wolfgang Arnoldd, Edgar Grinsteina, Arnfried Schwartza, Lope Estevéz-Schwarze, Peter M. Schlage, Brigitte M. Jockuschb, and Siegfried Schernecka
a Department of Medical Genetics, Max-Delbrück-Center for Molecular Medicine, 13092 Berlin-Buch, Germany
b Department of Cell Biology, Zoological Institute, Technical University of Braunschweig, 38106 Braunschweig, Germany
c Institute of Pathology, Charité Hospital, Humboldt University, 10117 Berlin, Germany
d HepaVec GmbH, 13125 Berlin-Buch, Germany
e Clinic of Surgery and Surgical Oncology, Robert Roessle Hospital, 13122 Berlin-Buch, Germany

Correspondence to: Siegfried Scherneck, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany. Tel:49-30-9406-2226 Fax:49-30-9406-3842 E-mail:sschern{at}mdc-berlin.de.

Differential display screening was used to reveal differential gene expression between the tumorigenic breast cancer cell line CAL51 and nontumorigenic microcell hybrids obtained after transfer of human chromosome 17 into CAL51. The human profilin 1 (PFN1) gene was found overexpressed in the microcell hybrid clones compared with the parental line, which displayed a low profilin 1 level. A comparison between several different tumorigenic breast cancer cell lines with nontumorigenic lines showed consistently lower profilin 1 levels in the tumor cells. Transfection of PFN1 cDNA into CAL51 cells raised the profilin 1 level, had a prominent effect on cell growth, cytoskeletal organization and spreading, and suppressed tumorigenicity of the stable, PFN1-overexpressing cell clones in nude mice. Immunohistochemical analysis revealed intermediate and low levels of profilin 1 in different human breast cancers. These results suggest profilin 1 as a suppressor of the tumorigenic phenotype of breast cancer cells.

Key Words: tumor suppressor genes, microcell hybrids, cytoskeleton, actin filament, differential display


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