Reduced growth of human breast cancer xenografts in hosts homozygous for the 'lit' mutation
Year: 1996
Type: article
Abstract: Insulin-like growth factor I (IGF-I) is a potent breast cancer mitogen.Growth hormone (GH) up-regulates hepatic /(./-/ gene expression and circulating IGF-I level.Tissue IGF bioactivity is influenced not only by circulating IGF-I and K.I -II levels but also by autocrine and paracrine production of these growth factors and by IGF binding proteins.There is considerable person-to-person variability in GH-IGF-I physiology.Both laboratory and epidemiológica!data are consistent with the hypothesis that the host GH-IGF-I axis influences breast cancer behavior, but such an effect has not been directly demonstrated.To determine whether breast cancer growth in an in vivo model is influenced by the host GH-IGF-I axis, we compared the growth of human MCF-7 breast cancer cells in control mice to that in mice homozygous for lit. a missense mutation resulting in loss of function of the pituitary GH-releasing hormone receptor and secondary suppression of GH and IGF-I.Breast cancer growth was sig nificantly reduced in lit/lit animals compared to control hosts [tumor size (mean ±SD) on day 39, 444 ±82 versus 845 ±444 mm3, respectively; P < 0.001, Mann-Whitney U test].These data demonstrate that in our model, host GH-IGF-I axis physiology plays a role in determining breast cancer behavior.The results « i suggest that patient-to-patient variability in GH-IGF-I physiology may contribute to the large variability between patients regarding breast cancer behavior, and b} motivate clinical trials of novel hormonal treatment strategies that target the GH-IGF-I axis.
Source: eScholarship@McGill (McGill)
Authors: Pollak, Michael N., Yang, Xiao-Feng, Beamer, Wesley G., Huynh, Hung
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G1778963489
OpenAlex ID: W6996270494