title: Interplay between steroid receptors and neoplastic progression in sarcoma tumors.
abstract: Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2) )/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells.
authors.affiliation: Thoracic Surgery Unit, Second University of Naples, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fiorelli
authors.forename: C
authors.initials: C
authors.lastname: Ricciardi
authors.forename: G
authors.initials: G
authors.lastname: Pannone
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: P
authors.initials: P
authors.lastname: Bufo
authors.forename: M
authors.initials: M
authors.lastname: Santini
authors.forename: R
authors.initials: R
authors.lastname: Serpico
authors.forename: R
authors.initials: R
authors.lastname: Rullo
authors.forename: G M
authors.initials: GM
authors.lastname: Pierantoni
authors.forename: M
authors.initials: M
authors.lastname: Di Domenico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008875:Middle Aged; D010865:Pilot Projects; D011987:Receptors, Steroid / Q000378:metabolism*; D012509:Sarcoma / Q000473:pathology*; D015398:Signal Transduction; D012983:Soft Tissue Neoplasms / Q000473:pathology*; D055815:Young Adult; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D011987:Receptors, Steroid; D015741:Metribolone; D004958:Estradiol; D066246:ErbB Receptors; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases