The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary             carcinoma cells.
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.
Liggins Institute, University of Auckland, Auckland 1023, New                     Zealand.
Lin
L
Hou
Bing
B
Xu
Kumarasamypet M
KM
Mohankumar
Vincent
V
Goffin
Jo K
JK
Perry
Peter E
PE
Lobie
Dong-Xu
DX
Liu
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D011388:Prolactin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099261:Homeobox A1 Protein
D018398:Homeodomain Proteins; D048052:Mitogen-Activated Protein Kinase 3; D011388:Prolactin; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; D000099261:Homeobox A1 Protein