title: Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland.
abstract: PTHrP is necessary for the formation of the embryonic mammary gland and, in its absence, the embryonic mammary bud fails to form the neonatal duct system. In addition, PTHrP is produced by the breast during lactation and contributes to the regulation of maternal calcium homeostasis during milk production. In this study, we examined the role of PTHrP during post-natal mammary development. Using a PTHrP-lacZ transgenic mouse, we surveyed the expression of PTHrP in the developing post-natal mouse mammary gland. We found that PTHrP expression is restricted to the basal cells of the gland during pubertal development and becomes expressed in milk secreting alveolar cells during pregnancy and lactation. Based on the previous findings that overexpression of PTHrP in cap and myoepithelial cells inhibited ductal elongation during puberty, we predicted that ablation of native PTHrP expression in the post-natal gland would result in accelerated ductal development. To address this hypothesis, we generated two conditional models of PTHrP-deficiency specifically targeted to the postnatal mammary gland. We used the MMTV-Cre transgene to ablate the floxed PTHrP gene in both luminal and myoepithelial cells and a tetracycline-regulated K14-tTA;tetO-Cre transgene to target PTHrP expression in just myoepithelial and cap cells. In both models of PTHrP ablation, we found that mammary development proceeds normally despite the absence of PTHrP. We conclude that PTHrP signaling is not required for normal ductal or alveolar development.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Kata
authors.initials: K
authors.lastname: Boras-Granic
authors.forename: Joshua
authors.initials: J
authors.lastname: VanHouten
authors.forename: Minoti
authors.initials: M
authors.lastname: Hiremath
authors.forename: John
authors.initials: J
authors.lastname: Wysolmerski
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression; D007774:Lactation; D008321:Mammary Glands, Animal / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D044162:Parathyroid Hormone-Related Protein / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D011247:Pregnancy; D014018:Tissue Distribution
chemical_list: D044162:Parathyroid Hormone-Related Protein
references.citation: BMC Genomics. 2008 Dec 08;9:591
references.pmid: 19063729
references.citation: Cancer Res. 2004 May 1;64(9):3037-45
references.pmid: 15126339
references.citation: Development. 2001 Feb;128(4):513-25
references.pmid: 11171335
references.citation: Transgenic Res. 2001 Dec;10(6):545-53
references.pmid: 11817542
references.citation: Development. 1999 Aug;126(16):3485-93
references.pmid: 10409496
references.citation: Development. 1995 Nov;121(11):3539-47
references.pmid: 8582268
references.citation: Endocrinology. 2003 Feb;144(2):407-11
references.pmid: 12538599
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1133-7
references.pmid: 7508121
references.citation: Arch Pathol Lab Med. 2011 Apr;135(4):422-9
references.pmid: 21466356
references.citation: J Clin Invest. 2003 Nov;112(9):1429-36
references.pmid: 14597768
references.citation: Dev Biol. 1998 Nov 1;203(1):75-89
references.pmid: 9806774
references.citation: Breast Cancer Res. 2006;8(1):201
references.pmid: 16524451
references.citation: Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a003251
references.pmid: 20484386
references.citation: Science. 1988 Oct 14;242(4876):278-80
references.pmid: 3175653
references.citation: J Bone Miner Res. 2006 Jan;21(1):113-23
references.pmid: 16355280
references.citation: Cancer Biol Ther. 2008 Jan;7(1):3-9
references.pmid: 18059174
references.citation: Cancer Res. 2009 Sep 15;69(18):7473-9
references.pmid: 19723659
references.citation: Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
references.pmid: 20926515
references.citation: Cell. 2006 Dec 1;127(5):1041-55
references.pmid: 17129787
references.citation: Cancer Res. 2006 Feb 15;66(4):2250-6
references.pmid: 16489028
references.citation: Eur J Cancer. 1995;31A(3):334-9
references.pmid: 7786598
references.citation: Development. 1998 Apr;125(7):1285-94
references.pmid: 9477327
references.citation: Endocrinology. 2003 Dec;144(12):5521-9
references.pmid: 14500568
references.citation: Nat Rev Genet. 2007 Dec;8(12):963-72
references.pmid: 18007652
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: J Endocrinol. 2001 Dec;171(3):403-16
references.pmid: 11739006
references.citation: Development. 2008 Mar;135(6):995-1003
references.pmid: 18296651
references.citation: Differentiation. 2006 Sep;74(7):365-81
references.pmid: 16916375
references.citation: J Clin Invest. 1996 Oct 1;98(7):1544-9
references.pmid: 8833902
references.citation: J Clin Endocrinol Metab. 2001 Apr;86(4):1788-94
references.pmid: 11297619
references.citation: Exp Cell Res. 2004 Apr 1;294(2):420-33
references.pmid: 15023531
references.citation: Physiol Rev. 2001 Jan;81(1):239-297
references.pmid: 11152759
references.citation: Dev Cell. 2001 Oct;1(4):467-75
references.pmid: 11703938