Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland
- PMID: 24505323
- PMCID: PMC3913705
- DOI: 10.1371/journal.pone.0087858
Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland
Abstract
Background: Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals.
Results: We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland.
Conclusion: Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.
Conflict of interest statement
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References
-
- Hennighausen L, Robinson GW (2001) Signaling pathways in mammary gland development. Dev Cell 1: 467–475. - PubMed
-
- Bocchinfuso WP, Korach KS (1997) Mammary gland development and tumorigenesis in estrogen receptor knockout mice. J Mammary Gland Biol Neoplasia 2: 323–334. - PubMed
-
- Howlin J, McBryan J, Martin F (2006) Pubertal mammary gland development: insights from mouse models. J Mammary Gland Biol Neoplasia 11: 283–297. - PubMed
-
- Humphreys RC, Lydon JP, O'Malley BW, Rosen JM (1997) Use of PRKO mice to study the role of progesterone in mammary gland development. J Mammary Gland Biol Neoplasia 2: 343–354. - PubMed
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