title: Association of fragile site-associated (FSA) gene expression with epithelial differentiation and tumor development.
abstract: A novel gene designated as fragile site-associated (FSA) gene was recently identified by positional cloning from the CHO 1q31 fragile site which plays an important role in regulating amplification of multidrug resistance (mdr1) gene in multidrug-resistant cells. FSA produces a message of approximately 16 kb which encodes an open-reading frame of 5005 amino acids. FSA shares sequence similarity with that in Caenorhabditis elegans lpd-3, a lipid storage gene. Using immunohistochemical staining and RNA in situ hybridization we report here that expression of FSA is associated with developmental programs of spermatogenesis and mammary gland in mice. Real-time RT-PCR results also support the upregulation of FSA expression in mammary gland development. Expression of FSA in many tissues including colon, skin, ovary, prostate, and bladder is mainly in the postmitotic, well-differentiated compartments. Moreover, levels of FSA expression are downregulated in tumors of these tissue origins. These results suggest that FSA also plays important roles in regulating mammalian epithelial growth and differentiation and tumor development.
authors.affiliation: Department of Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Street, Houston, TX 77030, USA. tkuo@mdanderson.org
authors.forename: M Tien
authors.initials: MT
authors.lastname: Kuo
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wei
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tatebe
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Stanly R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Niramol
authors.initials: N
authors.lastname: Savaraj
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D043283:Chromosome Fragile Sites; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008321:Mammary Glands, Animal; D051379:Mice; D008938:Mitosis; D016366:Open Reading Frames; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; C471933:lpd-3 protein, C elegans; D012313:RNA