Overexpression of P53 protein and local hGH, IGF-I, IGFBP-3, IGFBP-2 and PRL secretion by human breast cancer explants.
BACKGROUND: Insulin-like growth factor-I (IGF-I) in concert with insulin-like binding protein 3 (IGFBP-3), insulin-like binding protein 2 (IGFBP-2), human growth hormone (GH) and P53 protein is involved in autocrine/paracrine growth signaling pathways as an adaptive response to environmental stimuli.
OBJECTIVE: The study evaluated the local secretion of PRL, hGH, IGF-I, IGFBP-2 and IGFBP-3 by breast cancer tissue explants in relation to the overexpression of P53 protein in breast cancer tissue.
MATERIALS AND METHODS: Breast cancer explants were obtained during radical mastectomies. The overexpression of P53 protein was assessed immunohistochemically using monoclonal antibody (DAKO, Anti-Human P53 protein, clone DO-7); the results of the reaction were stratified into 5 groups. The lack of P53 protein overexpression was defined as 0% of cells that overexpressed P53 protein. IGF-I, IGFBP-3, IGFBP-2, and hGH levels were measured with RIA kits, and prolactin was measured with the MEIA kit.
RESULTS: The local secretion of hGH by tumour explants - presenting a positive immunohistochemical reaction (IHCR) to the product of P53 gene - was twice as high as those with no IHCR to product of P53 gene; the opposite was noted in the case of IGF-I, IGFBP-2 and IGFBP-3 secretion. In both cases, the level of hGH, IGF-I and IGFBP-3 secretion did not correlate with the ratio of cells overexpressing P53 protein. There was a significant decrease in local, basic IGFBP-2 secretion along with an increased ratio of cells with positive IHCR to product of P53 gene. Furthermore, local PRL secretion was not correlated with the ratio of cells overexpressing P53 protein in breast cancer tissue. Prolactin also exerts no influence on IGF-I secretion.
CONCLUSION: Our results may suggest the presence of local hGH/IGF-I feedback in breast tissue as well as the possibility of P53/hGH/IGF-I/IGFBP-3 but not P53/PRL/IGF-I axis....