Is there an association between uterine leiomyomas and acid phosphatase locus 1 polymorphism?

Published:November 07, 2008DOI:


      Platelet derived growth factor (PDGF) is involved in the development of leiomyomas. The low-molecular-weight phosphoprotein-tyrosine–phosphatase (LMWPTP), controlled by the highly polymorphic acid phosphatase locus 1 (ACP1), is able to dephosphorylate the PDGF receptor. Therefore, we searched for a possible association between ACP1 and leiomyomas.

      Study Design

      We studied 172 women hospitalized for symptomatic leiomyomas requiring surgical intervention and 164 healthy women without clinical evidence of leiomyomas from the same white population. The χ2 test of independence, Pearson correlation, analysis of variance, and post hoc test for difference between means were performed.


      The distribution of ACP1 genotypes among patients does not differ significantly from that of healthy women. However, leiomyoma size was negatively correlated with ACP1 F isoform concentrations. Leiomyoma size was smaller among carriers of the *B/*B genotype, which has the highest concentration of the F isoform, than among carriers of *A/*A, *C/*B, and *C/*C genotypes, which have the lowest concentration of the F isoform.


      High ACP1 F isoform concentration, through dephosphorylation of the PDGF receptor, may negatively regulate cell proliferation and growth of leiomyomas.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Flake G.P.
        • Andersen J.
        • Dixon D.
        Etiology and pathogenesis of uterine leiomyomas: a review.
        Environ Health Perspect. 2003; 111: 1037-1054
        • Parker W.H.
        Etiology, symptomatology, and diagnosis of uterine myomas.
        Fertil Steril. 2007; 87: 725-736
        • Stefani M.
        • Caselli A.
        • Bucciantini M.
        • et al.
        Dephosphorylation of tyrosine phosphorylated synthetic peptides by rat liver phosphotyrosine protein phosphatase isoenzymes.
        FEBS Lett. 1993; 326: 131-134
        • Bryson G.L.
        • Massa H.
        • Trask B.J.
        • Van Etten R.L.
        Gene structure, sequence, and chromosomal localization of the human red cell-type low-molecular-weight acid phosphotyrosyl phosphatase gene, ACP1.
        Genomics. 1995; 30: 133-140
        • Cirri P.
        • Fiaschi T.
        • Chiarugi P.
        • et al.
        The molecular basis of the differing kinetic behavior of the two low molecular mass phosphotyrosine protein phosphatase isoforms.
        J Biol Chem. 1996; 271: 2604-2607
        • Dissing J.
        • Rangaard B.
        • Christensen U.
        Activity modulation of the fast and slow isozymes of human cytosolic low-molecular-weight acid phosphates (ACP1) by purines.
        Biochim Biophys Acta. 1993; 1162: 275-282
        • Dissing J.
        • Johnsen A.H.
        • Sensabaugh G.F.
        Human red cell acid phosphatase (ACP1).
        J Biol Chem. 1991; 266: 20619-20625
        • Wo Y.Y.P.
        • McCormack A.L.
        • Shabanowitz J.
        • et al.
        Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase.
        J Biol Chem. 1992; 267: 10856-10865
        • Dissing J.
        • Johnsen A.H.
        Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles.
        Biochim Biophys Acta. 1992; 1121: 261-268
        • Lazaruk K.D.
        • Dissing J.
        • Sensabaugh G.F.
        Exon structure at the human ACP1 locus supports alternative splicing model for f and s isozyme generation.
        Biochem Biophys Res Commun. 1993; 196: 440-446
        • Hopkinson D.A.
        • Spencer N.
        • Harris H.
        Red cell acid phosphatase variants: a new human polymorphism.
        Nature. 1963; 199: 969-971
        • Sensabaugh G.F.
        • Lazaruk K.A.
        A Taq1 site identifies the *A allele at the ACP1 locus.
        Hum Mol Genet. 1993; 2: 1079
        • Dissing J.
        Immunochemical characterization of human red cell acid phosphatase isozymes.
        Biochem Genet. 1987; 25: 901-918
        • Ramponi G.
        • Ruggiero M.
        • Raugei G.
        • et al.
        Overexpression of a synthetic phosphotyrosine protein phosphatase gene inhibits normal and transformed cell growth.
        Int J Cancer. 1992; 51: 652-656
        • Ruggiero M.
        • Pazzagli C.
        • Rigacci S.
        • et al.
        Negative growth control by a novel low Mr phosphotyrosine protein phosphatase in normal and transformed cells.
        FEBS Lett. 1993; 326: 294-298
        • Berti A.
        • Rigacci S.
        • Raugei G.
        • Degl'Innocenti D.
        • Ramponi G.
        Inhibition of cellular response to platelet-derived growth factor by low Mr phosphotyrosine protein phosphatase overexpression.
        FEBS Lett. 1994; 394: 7-12
        • Chiarugi P.
        • Cirri P.
        • Marra F.
        • et al.
        LMW-PTP is a negative regulator of insulin-mediated mitotic and metabolic signalling.
        Biochem Biophys Res Commun. 1997; 238: 676-682
        • Ramponi G.
        • Manao G.
        • Camici G.
        • Cappugi G.
        • Ruggiero M.
        • Bottaio D.P.
        The 18 kDa cytosolic acid phosphatase from bovine liver has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor.
        FEBS Lett. 1989; 250: 469-473
        • Bottini N.
        • Stefanini L.
        • Williams S.
        • et al.
        Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP).
        J Biol Chem. 2002; 277: 24220-24224
        • Licato L.L.
        • Brenner D.A.
        Analysis of signalling protein kinase in human colon or colorectal carcinomas.
        Dig Dis Sci. 1998; 43: 1454-1464
        • Kobayashi M.
        • Iwamatsu A.
        • Shinohara-Kanda A.
        • Ihara S.
        • Fukui Y.
        Activation of ErbB3-PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas.
        Oncogene. 2003; 22: 1294-1301
        • La Forgia S.
        • Morse B.
        • Levj J.
        • et al.
        Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.
        Proc Natl Acad Sci USA. 1991; 88: 5036-5040
        • Fischer E.H.
        • Charbonneau H.
        • Tonks N.K.
        Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes.
        Science. 1991; 253: 401-406
        • Goldstein B.J.
        Protein-tyrosine phosphatases and the regulation of insulin action.
        J Cell Biochem. 1992; 48: 33-42
        • Lazaruk K.D.A.
        Molecular genetics of human red cell acid phosphatase.
        ([PhD dissertation]) University of California, Berkeley, CA1995
        • Kunkel L.M.
        • Smith K.D.
        • Boyer S.H.
        • et al.
        Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants.
        Proc Natl Acad Sci USA. 1977; 74: 1245-1249
        • Dissing J.
        Human “red cell” acid phosphatase (ACP1) genetic, catalytic and molecular properties.
        ([PhD thesis]) Copenhagen University, Copenhagen, Denmark1993
        • Bottini E.
        • Gloria-Bottini F.
        • Borgiani P.
        ACP1 and human adaptability.
        Hum Genet. 1995; 96: 629-637
        • Bottini N.
        • Bottini E.
        • Gloria-Bottini F.
        • Mustelin T.
        Low-molecular-weight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms.
        Arch Immunol Ther Exp (Warsz). 2002; 50: 95-104