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Originally published In Press as doi:10.1074/jbc.M101687200 on April 13, 2001

J. Biol. Chem., Vol. 276, Issue 25, 22954-22964, June 22, 2001
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Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-Delta N in Human Breast Cancer Cells*

Anne BoulayDagger , Catherine H. Régnier, Patrick Anglard, Isabelle Stoll, Catherine Tomasetto, and Marie-Christine Rio§

From the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U184/ULP BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France

An aberrant truncated hHb1 hair keratin transcript, named hHb1-Delta N, was previously identified in breast carcinomas. No normal tissue tested so far, including hairy skin, expressed hHb1-Delta N, indicating that hHb1-Delta N is related to carcinogenesis. In the present study, we investigated the mechanism by which such truncated transcript was generated in breast cancer cell lines. We found that hHb1-Delta N transcription is initiated at an unusual cryptic promoter within the fourth intron of the hHb1 gene and is dependent on two proximal Sp1 binding sites for its baseline activity. Moreover, hHb1-Delta N transcription is increased in response to DNA demethylation by the 5-aza-2'-deoxycytidine drug. This induction is dependent on protein neosynthesis, indicating that an additional factor is required. In addition, we showed that the hHb1-Delta N transcript is translated in vivo as a truncated hHb1 protein that is missing the 270 amino-terminal residues. The hHb1-Delta N protein exhibits a filament pattern throughout the cytoplasm and partially co-localizes with cytokeratin filaments, indicating its participation in the cytoskeleton network. hHb1-Delta N might alter the adhesive properties of cancer cells.

* This work was supported in part by funds from INSERM, CNRS, the Hôpital Universitaire de Strasbourg, the Bristol-Myers Squibb Pharmaceutical Research Institute, the Association pour la Recherche sur le Cancer, the Ligue Nationale Française contre le Cancer and the Comités du Haut-Rhin et du Bas-Rhin, and the Fondation de France.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Recipient of a Ligue Nationale Française contre le Cancer fellowship.

§ To whom correspondence should be addressed: Tel.: 33-3-88-65-34-24; Fax: 33-3-88-65-32-01; E-mail: rio@igbmc.u-strasbg.fr.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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