Role of human HGFIN/nmb in breast cancer.
BACKGROUND
HGFIN, previously identified as nmb, and its homolog osteoactivin are single transmembrane proteins that are expressed in differentiated immune cells. These proteins exhibit properties that could potentiate tumorigenesis or decrease invasiveness. These seemingly opposing roles of HGFIN suggest that this protein might be central to malignancies and might also behave as a tumor suppressor. Consistent with the reported roles for HGFIN is the fact that this gene is regulated by p53 through multiple binding sites in the 5' flanking region, and is expressed in osteoblasts.


METHODS
This study used siRNA to knock-out HGFIN in non-tumorigenic breast cells and ectopically expressed HGFIN in breast cancer cells. In addition, in situ hybridization studies analyzed primary breast tissues from archived breast surgeries. Reporter gene assays studied the untranslated exon 1 of HGFIN.


RESULTS
HGFIN expression led to reduced cell growth of breast cancer cells and reduced migration. At the molecular level, reporter gene analyses determined the untranslated exon 1 to be a negative regulator of the upstream enhancing effect. Ectopic expression of wild-type p53 in breast cancer cells that expressed endogenous mutant p53 resulted in increased HGFIN reporter gene activities.


CONCLUSIONS
As the majority of cancer cells have mutations in p53, further studies on the relationship between p53 and HGFIN expression, and its role in tumor genesis and bone invasion, might uncover novel therapy targets for breast and other cancers. The results show a central role for p53 in HGFIN expression, which appears to determine the behavior of the cancer cells.
Metz
Rebecca L
RL
Department of Medicine, UMDNJ-New Jersey Medical School, Newark, NJ, USA.
Patel
Prem S
PS
Hameed
Meera
M
Bryan
Margaret
M
Rameshwar
Pranela
P
D024506:5' Flanking Region / Q000235:genetics; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C503042:GPNMB protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53