This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Basyuk, E. Articles by Journot, L. Search for Related Content PubMed PubMed Citation Articles by Basyuk, E. Articles by Journot, L.

---

Cancer Genes and Genomics

The Candidate Tumor Suppressor Gene ZAC Is Involved in Keratinocyte Differentiation and Its Expression Is Lost in Basal Cell Carcinomas

¹ Institut de Génomique Fonctionnelle, CNRS-UMR5203, INSERM-U661, Université Montpellier 1, Université Montpellier 2; ² Institut de Génétique Moléculaire, CNRS-UMR5535, Université Montpellier 2; and ³ Laboratoire de Dermatologie Moléculaire, IURC, EA3754, Montpellier, France

Requests for reprints: Laurent Journot, Institut de Génomique Fonctionnelle, 141, rue de la cardonille, F-34094 Montpellier Cedex 5, France. Phone: 33-467-142-932; Fax: 33-467-542-432. E-mail: Laurent.Journot{at}igf.cnrs.fr

ZAC is a zinc finger transcription factor that induces apoptosis and cell cycle arrest in various cell lines. The corresponding gene is maternally imprinted and localized on chromosome 6q24-q25, a region harboring an unidentified tumor suppressor gene for a variety of solid neoplasms. ZAC expression is lost or down-regulated in some breast, ovary, and pituitary tumors and in an in vitro model of ovary epithelial cell transformation. In the present study, we examined ZAC expression in normal skin and found a high expression level in basal keratinocytes and a lower, more heterogeneous, expression in the first suprabasal differentiating layers of epidermis. In vitro, ZAC was up-regulated following induction of keratinocyte differentiation. Conversely, ZAC expression triggered keratinocyte differentiation as indicated by induction of involucrin expression. Interestingly, we found a dramatic loss of ZAC expression in basal cell carcinoma, a neoplasm characterized by a relatively undifferentiated morphology. In contrast, ZAC expression was maintained in squamous cell carcinomas that retain the squamous differentiated phenotype. Altogether, these data suggest a role for ZAC at an early stage of keratinocyte differentiation and further support its role in carcinogenesis.

This article has been cited by other articles:

				E. H. Jensen, J. M. Lewis, J. M. McLoughlin, M. D. Alvarado, A. Daud, J. Messina, S. Enkemann, T. J. Yeatman, V. K. Sondak, and A. I. Riker Down-Regulation of Pro-Apoptotic Genes is an Early Event in the Progression of Malignant Melanoma Ann. Surg. Oncol., April 1, 2007; 14(4): 1416 - 1423. [Abstract] [Full Text] [PDF]

				J. D. Lewis, L. A. Payton, J. G. Whitford, J. A. Byrne, D. I. Smith, L. Yang, and R. K. Bright Induction of Tumorigenesis and Metastasis by the Murine Orthologue of Tumor Protein D52 Mol. Cancer Res., February 1, 2007; 5(2): 133 - 144. [Abstract] [Full Text] [PDF]

				A. Hoffmann, T. Barz, and D. Spengler Multitasking C2H2 Zinc Fingers Link Zac DNA Binding to Coordinated Regulation of p300-Histone Acetyltransferase Activity. Mol. Cell. Biol., July 1, 2006; 26(14): 5544 - 5557. [Abstract] [Full Text] [PDF]