A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells.
A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroid-like structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.
Platica
Micsunica
M
Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA. mickey.platica@mssm.edu
Ivan
Elena
E
Holland
James F
JF
Ionescu
Alin
A
Chen
Sheryl
S
Mandeli
John
J
Unger
Pamela D
PD
Platica
Ovidiu
O
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics*; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010902:Pituitary Gland / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C483315:PDF protein, human; D011994:Recombinant Proteins