Mammary gland development pathway - Puberty (Stage 2 of 4) (WP2814)

Homo sapiens

The primary mammary gland persists until puberty, when it grows and becomes branched. This results in the formation of secondary mammary gland. ESR1 and NRIP1 co-regulates PGR, STAT5A and AREG, which control proliferation and differentiation during mammary gland development. NRIP1 is also required for ductal elongation, in both epithelial and in stromal compartments [ 1]. Estrogen may also execute its growth effect through EGF. Especially, ERBB2, an EGF receptor, may activate or inhibit the growth according to the stage of development. In puberty, ERBB2 impairs the mammary epithelial cell proliferation [ 2]. AP1 regulates postnatal mammary gland development, mainly in puberty. Some AP1-dependent genes are shown in the figure [ 3]. FOSL1 is a FOS family member. FOS family members dimerize with JUN family members to form AP1 complex. MYC and CCND1 are associated with cell proliferation. VIM is a component of intermediate filaments and FN1 are related to cell adhesion and migration. TIMP1 is a protease inhibitor.


Lab. Biodados UFMG , Kristina Hanspers , Elisa Cirillo , Denise Slenter , Egon Willighagen , and Eric Weitz


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Homo sapiens



Cell Type Ontology

milk secreting cell

Pathway Ontology

regulatory pathway


Label Type Compact URI Comment
DNA Metabolite chebi:16991
DNA Metabolite chebi:16991
PGR GeneProduct ensembl:ENSG00000082175
EGF GeneProduct ensembl:ENSG00000138798
ESR1 GeneProduct ensembl:ENSG00000091831
STAT5A GeneProduct ensembl:ENSG00000126561
ERBB2 GeneProduct ensembl:ENSG00000141736
FOSL1 GeneProduct ensembl:ENSG00000175592
AREG GeneProduct ensembl:ENSG00000109321
FN1 GeneProduct ensembl:ENSG00000115414
VIM GeneProduct ensembl:ENSG00000026025
NRIP1 GeneProduct ensembl:ENSG00000180530
MYC GeneProduct ncbigene:4609
TIMP1 GeneProduct ensembl:ENSG00000102265
CCND1 GeneProduct ensembl:ENSG00000110092


  1. Ductal growth is impeded in mammary glands of C-neu transgenic mice. Mukherjee S, Louie SG, Campbell M, Esserman L, Shyamala G. Oncogene. 2000 Dec 7;19(52):5982–7. PubMed Europe PMC Scholia
  2. The AP-1 transcription factor regulates postnatal mammary gland development. Shen Q, Zhang Y, Uray IP, Hill JL, Kim HT, Lu C, et al. Dev Biol. 2006 Jul 15;295(2):589–603. PubMed Europe PMC Scholia
  3. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals. Nautiyal J, Steel JH, Mane MR, Oduwole O, Poliandri A, Alexi X, et al. Development. 2013 Mar;140(5):1079–89. PubMed Europe PMC Scholia