The role for NES1 serine protease as a novel tumor suppressor.
Previously (Liu et al, Cancer Res., 56: 3371-3379, 1996), we isolated a novel serine protease-like gene--Normal Epithelial Cell Specific-1 (NES1)--that is expressed in normal mammary epithelial cells but is down-regulated in most breast cancer cell lines. Here, we demonstrate that stable expression of NES1 in the NES1-negative MDA-MB-231 breast cancer cell line suppressed the oncogenicity as revealed by inhibition of the anchorage-independent growth and tumor formation in nude mice. Fluorescence in situ hybridization localized the NES1 gene to chromosome 19q13.3, a region that contains genes for related proteases (including the prostate-specific antigen) and is rearranged in human cancers. Similar to breast cancer cell lines, prostate cancer cell lines also lacked NES1 mRNA and protein expression. Together, these results strongly suggest a tumor-suppressor role for NES1 in breast and prostate cancer.
Goyal
J
J
Department of Radiation Oncology, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Smith
K M
KM
Cowan
J M
JM
Wazer
D E
DE
Lee
S W
SW
Band
V
V
D000818:Animals; D000970:Antineoplastic Agents; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007610:Kallikreins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000737:chemistry; D012697:Serine Endopeptidases / Q000502:physiology*; D014162:Transfection
D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D009363:Neoplasm Proteins; C100936:KLK10 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases