02 BOOK OF ABSTRACTS .indd

Thioredoxin regulates Mta1 modulation of MMP-9
transcription in MDA-MB-231 breast cancer cells
Lucia Cappabianca 1 , Antonietta R. Farina 1 , Antonella Tacconelli 1 ,
Giuseppina De Santis 1 , Kathryn Tonissen 2 , Alberto Gulino 3 and
Andrew R. Mackay 1,*
1
Dept. of Experimental Medicine, University of L’Aquila, L’Aquila, Italy; 2 School of
Biomolecular Science, Griffith University, Australia; 3 Dept. of General Pathology, University
of Rome “La Sapienza”, Rome, Italy
The highly malignant human breast cancer cell line MDA-MB-231 exhibits
constitutive co-expression of invasion and metastasis-associated genes thioredoxin
(trx), matrix metalloproteinase (MMP)-9 and metastasis associated gene (Mta)-1,
which paradoxically is a repressor of MMP-9 transcriptional. Here, we identify a
functional link between trx and Mta1 proteins that affects Mta1 regulation of MMP-
9 transcription. We show that Mta1 is a substrate for trx and that trx stimulates and
dominant negative C32S/C35S mutated trx inhibits MMP-9 transcription in MDA-MB-
231 cells by a mechanism involving the regulation of Mta1/HDAC recruitment to
the MMP-9 promoter in vivo. The data helps to explain the nuclear localisation and
co-expression of Mta1 with MMP-9 in this highly malignant breast cancer cell line.
A potential therapeutic use for Trx inhibitors and regulators of HDAC activity in the
treatment of malignant breast cancer will be discussed.
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