Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations

Robynn V. Schillace, Amy Skinner, Rodney Pommier, Steven O'Neill, Patrick J. Muller, Arpana Naik, Juliana Hansen, Su Ellen Johnson Pommier

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Background: Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.Methods: BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.Results: Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.Conclusions: BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.

    Original languageEnglish (US)
    Article number733
    JournalBMC Cancer
    Volume14
    Issue number1
    DOIs
    StatePublished - Sep 30 2014

    Fingerprint

    Progesterone Receptors
    Interleukin-8
    Neoplastic Stem Cells
    Estrogen Receptors
    Interleukin-6
    Stem Cells
    Breast Neoplasms
    Estrogens
    Population
    Neoplasms
    Messenger RNA
    Gene Expression
    Tamoxifen
    Proteins
    Ligation
    Hormones
    Recurrence
    Polymerase Chain Reaction

    Keywords

    • Breast cancer
    • Estrogen receptor
    • Interleukin-6
    • Interleukin-8
    • Progesterone receptor
    • Protein
    • Proximity ligation assay
    • Stem cell

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research
    • Genetics
    • Medicine(all)

    Cite this

    Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations. / Schillace, Robynn V.; Skinner, Amy; Pommier, Rodney; O'Neill, Steven; Muller, Patrick J.; Naik, Arpana; Hansen, Juliana; Pommier, Su Ellen Johnson.

    In: BMC Cancer, Vol. 14, No. 1, 733, 30.09.2014.

    Research output: Contribution to journalArticle

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    title = "Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations",
    abstract = "Background: Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.Methods: BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.Results: Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.Conclusions: BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.",
    keywords = "Breast cancer, Estrogen receptor, Interleukin-6, Interleukin-8, Progesterone receptor, Protein, Proximity ligation assay, Stem cell",
    author = "Schillace, {Robynn V.} and Amy Skinner and Rodney Pommier and Steven O'Neill and Muller, {Patrick J.} and Arpana Naik and Juliana Hansen and Pommier, {Su Ellen Johnson}",
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    TY - JOUR

    T1 - Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations

    AU - Schillace, Robynn V.

    AU - Skinner, Amy

    AU - Pommier, Rodney

    AU - O'Neill, Steven

    AU - Muller, Patrick J.

    AU - Naik, Arpana

    AU - Hansen, Juliana

    AU - Pommier, Su Ellen Johnson

    PY - 2014/9/30

    Y1 - 2014/9/30

    N2 - Background: Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.Methods: BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.Results: Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.Conclusions: BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.

    AB - Background: Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.Methods: BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.Results: Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.Conclusions: BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.

    KW - Breast cancer

    KW - Estrogen receptor

    KW - Interleukin-6

    KW - Interleukin-8

    KW - Progesterone receptor

    KW - Protein

    KW - Proximity ligation assay

    KW - Stem cell

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    U2 - 10.1186/1471-2407-14-733

    DO - 10.1186/1471-2407-14-733

    M3 - Article

    VL - 14

    JO - BMC Cancer

    JF - BMC Cancer

    SN - 1471-2407

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    M1 - 733

    ER -