Cloning and characterization of the 5' flanking region of the HGFIN gene indicate a cooperative role among p53 and cytokine-mediated transcription factors: relevance to cell cycle regulation.

HGFIN, previously identified as nmb, and its homologs, osteoactivin are single transmembrane protein that is expressed in differentiated immune cells, and are linked to tumor progression. These dichotomous roles suggest that HGFIN could be linked to cell cycle regulation. We hypothesize that HGFIN is linked to different phases of cell cycle regulation via specific transcription factors. This study cloned and analyzed two fragments in the 5' flanking region of HGFIN: HGFIN-RM/2.0: 2.0 kb upstream of Exon 1; HGFIN-RM/1.5: 5' deletion (500 bp) of HGFIN-RM/2.0. Computer analyses indicated that HGFIN has unique upstream sequence with eight potential p53 sites. Electrophoretic mobility shift assay with Cy3-labeled PCR fragments indicated that p53 could interact with fragments encompassing p53 consensus regions. Reporter gene activities with HGFIN-RM/2.0 and HGFIN-RM/1.5 in cells with different p53 levels showed that p53 is relevant to HGFIN activities. Studies with modified T47D in which cytokine production was downregulated, but with p53 level similar to parental line showed synergism between p53 and mediators of cytokine in the regulation of HGFIN. In summary, p53 cooperate with cytokine-mediated transcription factors to regulate the expression of HGFIN.