title: The impact of progesterone on simultaneous, local secretion of IGFBP-3 and IGF-I [IGFBP-3/IGF-I index] by human malignant and non-malignant breast explants depends on tissue steroid receptor phenotype.
abstract: OBJECTIVE
  Insulin-like growth factor-I (IGF-I) is regarded as one of mammary tissue proliferative factors. Insulin-like growth factor binding protein-3 (IGFBP-3) limits the IGF-I binding potential to its receptor. That limits the IGF-I bioavailability. Recently experimental studies indicated that insulin-like growth factor binding proteins (IGFBPs) might have their own biological actions beyond their ability to regulate insulin-like growth factors (IGFs). Our earlier results showed the progesterone-induced rise in hGH and IGF secretion by human breast cancer explants.
  
  
  OBJECTIVE
  To determine the ability of progesterone to stimulate simultaneous local IGF-I and IGFBP-3 secretion by non-malignant and malignant mammary tissue collected from different receptor phenotype tumours.
  
  
  METHODS
  Explants from the tumour and surrounding normal non-malignant tissue were obtained during surging. Breast cancer explants were defined as: ER+ PR+; ER-PR-; ER+ PR-; and ER-PR+. Part of the explants was fixed in 10% buffered formalin for steroid receptor determination by immunohistochemistry. Other parts were cut into small pieces, weight and cultured in Parker medium (M199) supplemented with 5% of calf serum at 37 degrees C in an atmosphere containing 5% CO2 for 48 hours in control medium or with the addition of progesterone (10-7 M). Later media were collected for IGF-I and IGFBP-3 concentration analysis.
  
  
  RESULTS
  Progesterone increased (p < 0.01) IGFBP-3/IGF-I index in ER(-)PR(-) non-malignant tissue and decreased the IGFBP-3/IGF-I index in ER(-)PR(+), ER(+)PR(-) non-malignant explants. That increased the IGF-I bioavailability. Breast malignant explants showed the progesterone induced IGFBP-3/IGF-I index decrease. The decrease was most evident (p < 0.01) in malignant explants expressing progesterone receptor.
  
  
  CONCLUSIONS
  Progesterone increased local IGF-I bioavailability in malignant breast tissue. That phenomenon depended on steroid receptor phenotype of breast tissue and was most evident in tissue expressing progesterone receptor. In non-malignant tissue that phenomenon was also found in estrogen receptor expressing tissue. Lack of steroid receptor expression in breast explants reversed that phenomenon.
authors.affiliation: Kliniki Endokrynologii i Płodu Colledium Medicum Medicum UJ Kraków.
authors.forename: Józef
authors.initials: J
authors.lastname: Krzysiek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Milewicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Augustowska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sztefko
authors.forename: Janusz
authors.initials: J
authors.lastname: Ryś
authors.forename: Angela
authors.initials: A
authors.lastname: Zubel
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Pityński
authors.forename: Piotr
authors.initials: P
authors.lastname: Jaszczyński
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Herman
authors.forename: Antoni
authors.initials: A
authors.lastname: Basta
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stachura
authors.forename: Ewa Ł
authors.initials: EŁ
authors.lastname: Gregoraszczuk
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D010641:Phenotype; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen; D011374:Progesterone; D007334:Insulin-Like Growth Factor I