The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells

Int J Oncol. 2012 Dec;41(6):2285-95. doi: 10.3892/ijo.2012.1660. Epub 2012 Oct 15.


The HOX genes are a highly conserved subgroup of homeodomain-containing transcription factors that are crucial to normal development. Forced expression of HOXA1 results in oncogenic transformation of immortalized human mammary cells with aggressive tumour formation in vivo. Microarray analysis identified that the prolactin receptor (PRLR) was significantly upregulated by forced expression of HOXA1 in mammary carcinoma cells. To determine prolactin (PRL) involvement in HOXA1‑induced oncogenicity in mammary carcinoma cells (MCF-7), we examined the effect of human prolactin (hPRL)-initiated PRLR signal transduction on changes in cellular behaviour mediated by HOXA1. Forced expression of HOXA1 in MCF-7 cells increased PRLR mRNA and protein expression. Forced expression of HOXA1 also enhanced hPRL-stimulated phosphorylation of both STAT5A/B and p44/42 MAPK, and increased subsequent transcriptional activity of STAT5A and STAT5B, and Elk-1 and Sap1a, respectively. Moreover, forced expression of HOXA1 in MCF-7 cells enhanced the hPRL‑stimulated increase in total cell number as a consequence of enhanced cell proliferation and cell survival, and also enhanced hPRL-stimulated anchorage-independent growth in soft agar. Increased anchorage-independent growth was attenuated by the PRLR antagonist ∆1-9-G129R‑hPRL. In conclusion, we have demonstrated that HOXA1 increases expression of the cell surface receptor PRLR and enhances PRLR-mediated signal transduction. Thus, the PRLR is one mediator of HOXA1‑stimulated oncogenicity in mammary carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Prolactin / genetics
  • Prolactin / metabolism
  • Prolactin / pharmacology
  • Receptors, Prolactin / genetics
  • Receptors, Prolactin / metabolism*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Homeodomain Proteins
  • Receptors, Prolactin
  • STAT5 Transcription Factor
  • Transcription Factors
  • homeobox A1 protein
  • Prolactin
  • Mitogen-Activated Protein Kinase 3