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

  • Authors:
    • Lin Hou
    • Bing Xu
    • Kumarasamypet M. Mohankumar
    • Vincent Goffin
    • Jo K. Perry
    • Peter E. Lobie
    • Dong-Xu Liu
  • View Affiliations

  • Published online on: October 15, 2012     https://doi.org/10.3892/ijo.2012.1660
  • Pages: 2285-2295
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Abstract

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.
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December 2012
Volume 41 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hou L, Xu B, Mohankumar KM, Goffin V, Perry JK, Lobie PE and Liu D: The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells. Int J Oncol 41: 2285-2295, 2012.
APA
Hou, L., Xu, B., Mohankumar, K.M., Goffin, V., Perry, J.K., Lobie, P.E., & Liu, D. (2012). The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells. International Journal of Oncology, 41, 2285-2295. https://doi.org/10.3892/ijo.2012.1660
MLA
Hou, L., Xu, B., Mohankumar, K. M., Goffin, V., Perry, J. K., Lobie, P. E., Liu, D."The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells". International Journal of Oncology 41.6 (2012): 2285-2295.
Chicago
Hou, L., Xu, B., Mohankumar, K. M., Goffin, V., Perry, J. K., Lobie, P. E., Liu, D."The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells". International Journal of Oncology 41, no. 6 (2012): 2285-2295. https://doi.org/10.3892/ijo.2012.1660