Summary
Human growth hormone (hGH) is expressed by mammary epithelial cells and associated with proliferative disorders of the human breast. Our goal is to characterize the paracrine effects of hGH on morphological and functional changes of mammary carcinoma cells using MCF7 cells stably transfected with the hGH gene (MCFhGH). To identify the molecular actors involved in autocrine hGH-induced cell proliferation, we have used a protein chip technology using a commercial antibody microarray. The results enabled us to qualitatively characterize MCF-hGH cell’s proteome from a panel of 500 proteins. Statistical analysis of variations in protein levels between the two cell lines did not highlight any significant differences. Thus, we concluded that variations in MCF-hGH proteome are more likely to reside in the activation status rather than drastic variations in the expression level of the 500 spotted proteins. To test this hypothesis, we confronted the protein chip result to the study of the regulation of the transcriptional factor Pax (Paired-box)-5 whose expression was not found to be altered on the protein chip. Surprisingly, we found that autocrine production of hGH in MCF7 cells was associated with a strong nuclear accumulation of Pax5 in a JAK2-dependent manner associated with an increase in Pax5-DNA binding activity. Our work indicates that subtle changes mediated by Pax5 are responsible for autocrine hGH-induced cell proliferation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Mukhina S, Liu D, Guo K, et al. (2006) Autocrine growth hormone prevents lactogenic differentiation of mouse mammary epithelial cells. Endocrinology 147:1819–1829.
Raccurt M, Lobie PE, Moudilou E, et al. (2002) High stromal and epithelial human GH gene expression is associated with proliferative disorders of the mammary gland. J Endocrinol 175:307–318.
Zhu T, Starling-Emerald B, Zhang X, et al. (2005) Oncogenic transformation of human mammary epithelial cells by autocrine human growth hormone. Cancer Res 65:317–324.
Mukhina S, Mertani HC, Guo K, et al. (2004) Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone. Proc Natl Acad Sci USA 101:15166–15171.
Mertani HC, Zhu T, Goh EL, et al. (2001) Autocrine human growth hormone (hGH) regulation of human mammary carcinoma cell gene expression. Identification of CHOP as a mediator of hGH-stimulated human mammary carcinoma cell survival. J Biol Chem 276:21464–21475.
Zhang X, Zhu T, Chen Y, et al. (2003) Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. J Biol Chem 278:7580–7590.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer
About this chapter
Cite this chapter
Vouyovitch, C.M. et al. (2008). Proteomic Analysis of Autocrine/Paracrine Effects of Human Growth Hormone in Human Mammary Carcinoma Cells. In: Li, J.J., Li, S.A., Mohla, S., Rochefort, H., Maudelonde, T. (eds) Hormonal Carcinogenesis V. Advances in Experimental Medicine and Biology, vol 617. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69080-3_49
Download citation
DOI: https://doi.org/10.1007/978-0-387-69080-3_49
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-69078-0
Online ISBN: 978-0-387-69080-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)