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
Krzysiek, J.óz.; Milewicz, T.; Augustowska, K.; Sztefko, K.; Ryś, J.; Zubel, A.; Pityński, K.; Jaszczyński, P.; Herman, K.; Basta, A.; Stachura, J.; Gregoraszczuk, E.Ł
Ginekologia Polska 74(9): 767-774
2003
ISSN/ISBN: 0017-0011 PMID: 14674122 Document Number: 559640
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. 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. 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. 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. 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.