Karen M M Kelley

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The IGFBPs are a family of homologous proteins that have co-evolved with the IGFs and that confer upon the IGF regulatory system both functional and tissue specificity. IGFBPs are not merely carrier proteins for IGFs, but hold a central position in IGF ligand-receptor interactions through influences on both the bioavailability and distribution of IGFs in(More)
Retinoic acid (RA) is a potent in vitro inhibitor of cell proliferation in various malignant cell lines. The exact mechanisms of its actions, however, are not fully understood. To further elucidate the nature of this inhibition, we investigated the effects of RA in an estrogen receptor-negative human breast cancer cell line, MDA-MB-231. RA (0.01-5 microM)(More)
The human folate receptor (hFR) type gamma gene is driven by a TATA-less promoter that uses a canonical Sp1 element for basal transcription. Using nuclear extract from 293 (human embryonic) cells, we mapped a second (non-canonical) Sp1 element to which Sp1 bound with a comparable affinity and which overlaps a functional ets binding site (EBS). Mutagenesis(More)
The folate receptor (FR) type alpha is a promising target for diagnostic imaging agents and therapeutic intervention in major subtypes of gynecological malignancies; however, the receptor levels in the tumors are variable and are generally relatively low in estrogen receptor (ER)-positive tumors. Here we report that the FR-alpha gene promoter is repressed(More)
Both articular cartilage and the central nervous system are target organs for insulin-like growth factors (IGFs). We have previously described the hormonal regulation of IGF binding proteins (IGFBPs) in the conditioned media (CM) of rat articular chondrocytes and in a rat neuroblastoma cell line (B104). In the studies presented here, we have investigated(More)
The folate receptor α (FRα) is critical for normal embryonic and fetal development. The receptor has a relatively narrow tissue specificity which includes the visceral endoderm and the placenta and mediates delivery of folate, inadequacy of which results in termination of pregnancy or developmental defects. We have previously reported that the FRα gene is(More)
Estradiol (E2) acts through the estrogen receptor (ER) to downregulate many genes, and tamoxifen (Tam) largely reverses this repression but the underlying mechanisms are unclear. Repression of the folate receptor (FR)-α P4 core promoter by ER is enhanced by E2 and reversed by Tam. This effect was unaffected by inhibition of new protein synthesis and(More)
INTRODUCTION Adolescence is a time of physical, emotional and social transitions that have implications for health. In addition to being at high risk for HIV, young key populations (YKP) may experience other health problems attributable to high-risk behaviour or their developmental stage, or a combination of both. METHODS We reviewed the needs, barriers(More)
The utility of the folate receptor (FR) type alpha, in a broad range of targeted therapies and as a diagnostic serum marker in cancer, is confounded by its variable tumor expression levels. FR-alpha, its mRNA and its promoter activity were coordinately up-regulated by the glucocorticoid receptor (GR) agonist, dexamethasone. Optimal promoter activation which(More)