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.
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.
Krzysiek
Józef
J
Kliniki Endokrynologii i Płodu Colledium Medicum Medicum UJ Kraków.
Milewicz
Tomasz
T
Augustowska
Katarzyna
K
Sztefko
Krystyna
K
Ryś
Janusz
J
Zubel
Angela
A
Pityński
Kazimierz
K
Jaszczyński
Piotr
P
Herman
Krzysztof
K
Basta
Antoni
A
Stachura
Jerzy
J
Gregoraszczuk
Ewa Ł
EŁ
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
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