Progesterone-inducible cytokeratin 5-positive cells in luminal breast cancer exhibit progenitor properties.

Progestins play a deleterious role in the onset of breast cancer, yet their influence on existing breast cancer and tumor progression is not well understood. In luminal estrogen receptor (ER)- and progesterone receptor (PR)-positive breast cancer, progestins induce a fraction of cells to express cytokeratin 5 (CK5), a marker of basal epithelial and progenitor cells in the normal breast. CK5(+) cells lose expression of ER and PR and are relatively quiescent, increasing their resistance to endocrine and chemotherapy compared to intratumoral CK5(-)ER(+)PR(+) cells.

A high-content assay to identify small-molecule modulators of a cancer stem cell population in luminal breast cancer.

Breast cancers expressing hormone receptors for estrogen (ER) and progesterone (PR) represent ~70% of all cases and are treated with both ER-targeted and chemotherapies, with near 40% becoming resistant. We have previously described that in some ER(+) tumors, the resistant cells express cytokeratin 5 (CK5), a putative marker of breast stem and progenitor cells. CK5(+) cells have lost expression of ER and PR, express the tumor-initiating cell surface marker CD44, and are relatively quiescent.

Progesterone regulation of stem and progenitor cells in normal and malignant breast.

Progesterone plays an important, if not controversial, role in mammary epithelial cell proliferation and differentiation. Evidence supports that progesterone promotes rodent mammary carcinogenesis under some conditions, progesterone receptors (PR) are necessary for murine mammary gland tumorigenesis, and exogenous progestin use in post-menopausal women increases breast cancer risk. Thus, the progesterone/PR signaling axis can promote mammary tumorigenesis, albeit in a context-dependent manner.

HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes.

HOX (homeobox) genes encode homeodomain-containing transcription factors critical to development, differentiation, and homeostasis. Their dysregulation has been implicated in a variety of cancers. Previously, we showed that a subset of genes of the HOXC cluster is upregulated in primary prostate tumors, lymph node metastases, and malignant prostate cell lines.