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 Li, H. Articles by DiRenzo, J. Search for Related Content PubMed PubMed Citation Articles by Li, H. Articles by DiRenzo, J.

Nestin Is Expressed in the Basal/Myoepithelial Layer of the Mammary Gland and Is a Selective Marker of Basal Epithelial Breast Tumors

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire; ² Departments of Pharmacology and Toxicology and Genetics, Dartmouth Medical School, Norris Cotton Cancer Center; ³ Department of Pathology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire; and ⁴ Medical Science Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Requests for reprints: James DiRenzo, Department of Pharmacology and Toxicology, Dartmouth Medical School, 7650 Remsen, Hanover, NH 03755. Phone: 603-650-1794; Fax: 603-650-1129; E-mail: james.direnzo{at}dartmouth.edu.

Transcriptional profiling has identified five breast cancer subtypes, of which the basal epithelial is most aggressive and correlates with poor prognosis. These tumors display a high degree of cellular heterogeneity and lack established molecular targets, such as estrogen receptor-, progesterone receptor, and Her2 overexpression, indicating a need for definitive diagnostic markers. We present evidence that nestin, a previously described marker of regenerative cells in diverse tissues, is expressed in the regenerative compartment of the normal human mammary gland. Colocalization studies indicate two distinct populations of mammary epithelia that express nestin: one expressing cytokeratin 14 (CK14) and N-p63 and another expressing desmin. Immunohistochemical analysis indicates that N-p63 and nestin are coordinately expressed during pregnancy in the murine mammary gland. In the embryonal carcinoma cell line NT2/D1, ectopic N-p63- disrupts retinoic acid–induced differentiation, thereby preserving expression of nestin; however, small interfering RNA–mediated ablation of nestin is insufficient to promote differentiation, indicating that whereas nestin may identify cells within the regenerative compartment of the mammary gland, it is insufficient to block differentiation and preserve replicative capacity. Immunohistochemical analysis of basal epithelial breast tumors, including those shown to carry BRCA1 mutations, indicates robust expression of nestin and CK14, punctate expression of p63, and low to undetectable levels of desmin expression. Nestin was not detected in other breast cancer subtypes, indicating selectivity for basal epithelial breast tumors. These studies identify nestin as a selective marker of the basal breast cancer phenotype, which displays features of mammary progenitors. [Cancer Res 2007;67(2):501–10]

This article has been cited by other articles:

				E. A. Rakha, J. S. Reis-Filho, and I. O. Ellis Basal-Like Breast Cancer: A Critical Review J. Clin. Oncol., May 20, 2008; 26(15): 2568 - 2581. [Abstract] [Full Text] [PDF]

				N. Li, S. Singh, P. Cherukuri, H. Li, Z. Yuan, L. W. Ellisen, B. Wang, D. Robbins, and J. DiRenzo Reciprocal Intraepithelial Interactions Between TP63 and Hedgehog Signaling Regulate Quiescence and Activation of Progenitor Elaboration by Mammary Stem Cells Stem Cells, May 1, 2008; 26(5): 1253 - 1264. [Abstract] [Full Text] [PDF]

				L. F. Sempere, M. Christensen, A. Silahtaroglu, M. Bak, C. V. Heath, G. Schwartz, W. Wells, S. Kauppinen, and C. N. Cole Altered MicroRNA Expression Confined to Specific Epithelial Cell Subpopulations in Breast Cancer Cancer Res., December 15, 2007; 67(24): 11612 - 11620. [Abstract] [Full Text] [PDF]