Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors

Hua Li, Pratima Cherukuri, Na Li, Victoria Cowling, Michael Spinella, Michael Cole, Andrew K Godwin, Wendy Wells, James DiRenzo

    Research output: Contribution to journalArticle

    92 Citations (Scopus)

    Abstract

    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-a, 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-a 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.
    Original languageEnglish
    Pages (from-to)501-10
    Number of pages10
    JournalCancer Research
    Volume67
    Issue number2
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    Nestin
    Human Mammary Glands
    Breast Neoplasms
    Keratin-14
    Desmin
    Breast
    Embryonal Carcinoma Stem Cells
    Progesterone Receptors
    Tretinoin
    Estrogen Receptors
    Small Interfering RNA
    Epithelium
    Phenotype
    Cell Line
    Pregnancy
    Mutation

    Cite this

    Li, Hua ; Cherukuri, Pratima ; Li, Na ; Cowling, Victoria ; Spinella, Michael ; Cole, Michael ; Godwin, Andrew K ; Wells, Wendy ; DiRenzo, James. / Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. In: Cancer Research. 2007 ; Vol. 67, No. 2. pp. 501-10.
    @article{be5103be806c4f3a81849168d848817d,
    title = "Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors",
    abstract = "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-a, 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-a 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.",
    author = "Hua Li and Pratima Cherukuri and Na Li and Victoria Cowling and Michael Spinella and Michael Cole and Godwin, {Andrew K} and Wendy Wells and James DiRenzo",
    year = "2007",
    doi = "10.1158/0008-5472.CAN-05-4571",
    language = "English",
    volume = "67",
    pages = "501--10",
    journal = "Cancer Research",
    issn = "0008-5472",
    publisher = "American Association for Cancer Research",
    number = "2",

    }

    Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. / Li, Hua; Cherukuri, Pratima; Li, Na; Cowling, Victoria; Spinella, Michael; Cole, Michael; Godwin, Andrew K; Wells, Wendy; DiRenzo, James.

    In: Cancer Research, Vol. 67, No. 2, 2007, p. 501-10.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors

    AU - Li, Hua

    AU - Cherukuri, Pratima

    AU - Li, Na

    AU - Cowling, Victoria

    AU - Spinella, Michael

    AU - Cole, Michael

    AU - Godwin, Andrew K

    AU - Wells, Wendy

    AU - DiRenzo, James

    PY - 2007

    Y1 - 2007

    N2 - 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-a, 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-a 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.

    AB - 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-a, 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-a 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.

    U2 - 10.1158/0008-5472.CAN-05-4571

    DO - 10.1158/0008-5472.CAN-05-4571

    M3 - Article

    C2 - 17234757

    VL - 67

    SP - 501

    EP - 510

    JO - Cancer Research

    JF - Cancer Research

    SN - 0008-5472

    IS - 2

    ER -