Abstract
The polymeric immunoglobulin receptor (PIGR) mediates transport of IgA and IgM antibodies across mucosal and glandular epithelia. Several studies have utilized immunohistochemistry to demonstrate that PIGR expression varies in different types of lung carcinoma, and is down-regulated during tumor progression. We have previously shown in cultured tumor cell-lines that basal transcription of the PIGR gene is regulated by the transcription factors USF1, USF2 and AP2. To examine the mechanism by which PIGR expression is down-regulated in lung carcinoma, RNA was microdissected from formalin-fixed, paraffin-embedded lung carcinomas (14 adenocarcinomas and 8 squamous cell carcinomas). Levels of PIGR, USF1, USF2 and AP2-α mRNA were quantified by real-time reverse transcriptase–polymerase chain reaction and normalized to mRNA for the housekeeping gene GAPDH. PIGR mRNA levels were decreased in adenocarcinomas and squamous cell carcinomas relative to adjacent non-tumor tissue, and were inversely correlated with stage of differentiation. USF1 and USF2 mRNA levels were reduced in adenocarcinomas relative to non-tumor tissue, while AP2-α levels were elevated. Multivariate regression analysis demonstrated that reduced USF2 mRNA and increased AP2-α mRNA levels were predictive of down-regulated PIGR mRNA expression in the majority of adenocarcinomas and in moderately differentiated squamous cell carcinomas.
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References
K Mostov C.S. Kaetzel (1999) Immunoglobulin transport and the polymeric immunoglobulin receptor. P.L. Ogra J. Mestecky M.E. Lamm W. Strober J.R. McGhee J. Bienenstock (Eds) Mucosal Immunology Academic Press, Inc. New York 181–211
I.N. Norderhaug F.E. Johansen H. Schjerven P. Brandtzaeg (1999) ArticleTitleRegulation of the formation and external transport of secretory immunoglobulins Crit. Rev. Immunol 19 481–508
J.P. Harris M.A. South (1981) ArticleTitleSecretory component: a glandular epithelial cell marker Am. J. Pathol. 105 47–53
C.G. Espinoza J.U. Balis S.R. Saba J.E. Paciga S.A. Shelley (1984) ArticleTitleUltrastructural and immunohistochemical studies of bronchiolo-alveolar carcinoma Cancer 54 2182–2189
H. Loosli J. Hurlimann (1984) ArticleTitleImmunohistological study of malignant diffuse mesotheliomas of the pleura Histopathology 8 793–803
A. Kondi-Paphitis B.J. Addis (1986) ArticleTitleSecretory component in pulmonary adenocarcinoma and mesothelioma Histopathology 10 1279–1287
H. Popper G. Wirnsberger H. Hoefler H. Denk (1987) ArticleTitleImmunohistochemical and histochemical markers of primary lung cancer, lung metastases, and pleural mesotheliomas Cancer Detect. Prev. 10 167–174
T. Kawai C. Torikata M. Suzuki (1988) ArticleTitleImmunohistochemical study of pulmonary adenocarcinoma Am. J. Clin. Pathol. 89 455–462
R.W. Brown G.M. Clark A.K. Tandon D.C. Allred (1993) ArticleTitleMultiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma Hum. Pathol. 24 347–354
P.M. Hempen K.M. Phillips P.S. Conway K.H. Sandoval T.A. Schneeman H.J. Wu C.S. Kaetzel (2002) ArticleTitleTranscriptional regulation of the human polymeric Ig receptor gene: Analysis of basal promoter elements J. Immunol. 169 1912–1921
M.E.C. Bruno R.B. West T.A. Schneeman E.H. Bresnick C.S. Kaetzel (2004) ArticleTitleUpstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene Mol. Immunol. 40 695–708
W.A. Franklin (2000) ArticleTitleDiagnosis of lung cancer: pathology of invasive and preinvasive neoplasia Chest 117 80S–89S
P. Brandtzaeg F.L. Jahnsen I.N. Farstad (1996) ArticleTitleImmune functions and immunopathology of the mucosa of the upper respiratory pathways Acta Otolaryngol. (Stockh) 116 149–159
K.J. Kim A.B. Malik (2003) ArticleTitleProtein transport across the lung epithelial barrier Am. J. Physiol. Lung Cell. Mol. Physiol. 284 L247–L259
R.D. Rossen M. Morgan K.C. Hsu W.T. Butler H.M. Rose (1968) ArticleTitleLocalization of 11 S external secretory IgA by immunofluorescence in tissues lining the oral and respiratory passages in man J. Immunol. 100 706–717
D.R. Tourville R.H. Adler J. Bienenstock T.B. Tomasi SuffixJr. (1969) ArticleTitleThe human secretory immunoglobulin system immunohistological localization of gamma A, secretory piece and lactoferrin in normal human tissues J. Exp. Med. 129 411–429
P. Brandtzaeg (1974) ArticleTitleMucosal and glandular distribution of immunoglobulin components: differential localization of free and bound SC in secretory epithelial cells J. Immunol. 112 1553–1559
P Brandtzaeg (1984) Immune functions of human nasal mucosa and tonsils in health and disease. J. Bienenstock (Eds) Immunology of the Lung and Upper Respiratory Tract. McGraw-Hill Book Co. New York 28–95
M.A. Fiedler C.S. Kaetzel P.B. Davis (1991) ArticleTitleSustained production of secretory component by human tracheal epithelial cells in primary culture Am. J. Physiol. (Lung Cell Mol. Physiol.) 261 L255–L261
W.E. Finkbeiner S.D. Carrier C.E. Teresi (1993) ArticleTitleReverse transcription-polymerase chain reaction (RT-PCR) phenotypic analysis of cell cultures of human tracheal epithelium, tracheobronchial glands, and lung carcinomas Am. J. Respir. Cell. Mol. Biol. 9 547–556
M. Rossel E. Brambilla M. Billaud D.A. Vuitton F. Blanc-Jouvan S. Biichle J.P. Revillard (1993) ArticleTitleNonspecific increased serum levels of secretory component in lung tumors: Relationship to the gene expression of the transmembrane receptor form Am. J. Respir. Cell. Mol. Biol. 9 341–346
M.E. Perry (1994) ArticleTitleThe specialised structure of crypt epithelium in the human palatine tonsil and its functional significance J. Anat. 185 111–127
T. Ferkol J.C. Perales E. Eckman C.S. Kaetzel R.W. Hanson P.B. Davis (1995) ArticleTitleGene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor J. Clin. Invest. 95 493–502
I. Gehrke R. Pabst (1990) ArticleTitleThe epithelium overlying rabbit bronchus-associated lymphoid tissue does not express the secretory component of immunoglobulin A Cell Tissue Res. 259 397–399
F. Lewis N.J. Maughan V. Smith K. Hillan P. Quirke (2001) ArticleTitleUnlocking the archive–gene expression in paraffin-embedded tissue J. Pathol. 195 66–71
Y. Shirota J. Stoehlmacher J. Brabender Y.P. Xiong H. Uetake K.D. Danenberg S. Groshen D.D. Tsao-Wei P.V. Danenberg H.J. Lenz (2001) ArticleTitleERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy J. Clin. Oncol. 19 4298–4304
S. Lassmann M. Bauer R. Soong J. Schreglmann K. Tabiti J. Nahrig R. Ruger H. Hofler M. Werner (2002) ArticleTitleQuantification of CK20 gene and protein expression in colorectal cancer by RT-PCR and immunohistochemistry reveals inter- and intratumour heterogeneity J. Pathol. 198 198–206
J.G. Einspahr R.S. Krouse J.M. Yochim P.V. Danenberg K.D. Danenberg A.K. Bhattacharyya M.E. Martinez D.S. Alberts (2003) ArticleTitleAssociation between cyclooxygenase expression and colorectal adenoma characteristics Cancer Res. 63 3891–3893
M. Kornmann W. Schwabe S. Sander M. Kron J. Strater S. Polat E. Kettner H.F. Weiser W. Baumann H. Schramm P. Hausler K. Ott D. Behnke L. Staib H.G. Beger K.H. Link (2003) ArticleTitleThymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil Clin. Cancer Res. 9 4116–4124
H.R. Kim R. Christensen N.H. Park P. Sapp M.K. Kang N.H. Park (2001) ArticleTitleElevated expression of hTERT is associated with dysplastic cell transformation during human oral carcinogenesis in situ Clin. Cancer Res. 7 3079–3086
E. Rosivatz I. Becker K. Specht E. Fricke B. Luber R. Busch H. Hofler K.F. Becker (2002) ArticleTitleDifferential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer Am. J. Pathol. 161 1881–1891
J. Fellenberg A. Krauthoff K. Pollandt G. Delling D. Parsch (2004) ArticleTitleEvaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue Lab. Invest. 84 113–121
H.N. Abrahamsen T. Steiniche E. Nexo S.J. Hamilton-Dutoit B.S. Sorensen (2003) ArticleTitleTowards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients J. Mol. Diagn. 5 34–41
K.E. Bijwaard N.S. Aguilera Y. Monczak M. Trudel J.K. Taubenberger J.H. Lichy (2001) ArticleTitleQuantitative real-time reverse transcription-PCR assay for cyclin D1 expression: utility in the diagnosis of mantle cell lymphoma Clin. Chem. 47 195–201
K. Specht M. Kremer U. Muller S. Dirnhofer M. Rosemann H. Hofler (2002) ArticleTitleQuintanilla-Martinez L and Fend F., Identification of cyclin D1 mRNA overexpression in B-cell neoplasias by real-time reverse transcription-PCR of microdissected paraffin sections. Clin. Cancer Res. 8 2902–2911
V.A. Thomazy R. Luthra M.O. Uthman P.J. Davies L.J. Medeiros (2002) ArticleTitleDetermination of cyclin D1 and CD20 mRNA levels by real-time quantitative RT-PCR from archival tissue sections of mantle cell lymphoma and other non-Hodgkin’s lymphomas J. Mol. Diagn. 4 201–208
O. Bock U. Lehmann H. Kreipe (2003) ArticleTitleQuantitative intra-individual monitoring of BCR-ABL transcript levels in archival bone marrow trephines of patients with chronic myeloid leukemia J. Mol. Diagn. 5 54–60
L. Quintanilla-Martinez M. Kremer K. Specht J. Calzada-Wack M. Nathrath R. Schaich H. Hofler F. Fend (2003) ArticleTitleAnalysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events Am. J. Pathol. 162 1449–1461
J.L. Traicoff L. DeMarchis B.L. Ginsburg R.E. Zamora N.H. Khattar V.J. Blanch S. Plummer S.A. Bargo D.J. Templeton G. Casey C.S. Kaetzel (2003) ArticleTitleCharacterization of the human polymeric immunoglobulin receptor (PIGR) 3’UTR and differential expression of PIGR mRNA during colon tumorigenesis J. Biomed. Sci. 10 792–804
F.E. Johansen B.A. Bosloven P. Krajci P. Brandtzaeg (1998) ArticleTitleA composite DNA element in the promoter of the polymeric immunoglobulin receptor regulates its constitutive expression Eur. J. Immunol. 28 1161–1171
R.S. Solorzano-Vargas J. Wang L. Jiang H.V. Tsai L.O. Ontiveros M.A. Vazir R.J. Aguilera M.G. Martín (2002) ArticleTitleMultiple transcription factors in 5’-flanking region of human polymeric Ig receptor control its basal expression Am. J. Physiol. Gastrointest. Liver Physiol. 283 415–425
H. Beckmann L.-K. Su T. Kadesch (1990) ArticleTitleTFE3: A helix-loop-helix protein that activates transcription through the immunoglobulin enhancer μE3 motif Genes Dev. 4 167–179
D.E. Fisher C.S. Carr L.A. Parent P.A. Sharp (1991) ArticleTitleTFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family Genes Dev. 5 2342–2352
J.L. Meier X. Luo M. Sawadogo S.E. Straus (1994) ArticleTitleThe cellular transcription factor USF cooperates with varicella-zoster virus immediate-early protein 62 to symmetrically activate a bidirectional viral promoter Mol. Cell. Biol. 14 6896–6906
M. Sirito Q. Lin J.M. Deng R.R. Behringer M. Sawadogo (1998) ArticleTitleOverlapping roles and asymmetrical cross-regulation of the USF proteins in mice Proc. Natl. Acad. Sci. USA 95 3758–3763
A. Kiermaier J.M. Gawn L. Desbarats R. Saffrich W. Ansorge P.J. Farrell M. Eilers G. Packham (1999) ArticleTitleDNA binding of USF is required for specific E-box dependent gene activation in vivo Oncogene 18 7200–7211
B. Lüscher L.G. Larsson (1999) ArticleTitleThe basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: function and regulation Oncogene 18 2955–2966
M. Sawadogo (1988) ArticleTitleMultiple forms of the human gene-specific transcription factor USF I.I. DNA binding properties and transcriptional activity of the purified HeLa USF. J. Biol. Chem. 263 11994–12001
P.D. Gregor M. Sawadogo R.G. Roeder (1990) ArticleTitleThe adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer Genes Dev. 4 1730–1740
M. Sirito S. Walker Q. Lin M.T. Kozlowski W.H. Klein M. Sawadogo (1992) ArticleTitleMembers of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers Gene Expr. 2 231–240
B.J. Kirschbaum P. Pognonec R.G. Roeder (1992) ArticleTitleDefinition of the transcriptional activation domain of recombinant 43-kilodalton USF Mol. Cell. Biol. 12 5094–5101
M. Sirito Q. Lin T. Maity M. Sawadogo (1994) ArticleTitleUbiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells Nucleic Acids Res. 22 427–433
X. Luo M. Sawadogo (1996) ArticleTitleAntiproliferative properties of the USF family of helix-loop-helix transcription factors Proc. Natl. Acad. Sci. USA 93 1308–1313
E. Cheung P. Mayr F. Coda-Zabetta P.G. Woodman D.S. Boam (1999) ArticleTitleDNA-binding activity of the transcription factor upstream stimulatory factor 1 (USF-1) is regulated by cyclin-dependent phosphorylation Biochem. J. 344 Pt 1 145–152
S. North X. Espanel F. Bantignies B. Viollet V. Vallet P. Jalinot G. Brun G. Gillet (1999) ArticleTitleRegulation of cdc2 gene expression by the upstream stimulatory factors (USFs) Oncogene 18 1945–1955
Y. Qyang X. Luo T. Lu P.M. Ismail D. Krylov C. Vinson M. Sawadogo (1999) ArticleTitleCell-type-dependent activity of the ubiquitous transcription factor USF in cellular proliferation and transcriptional activation Mol. Cell. Biol. 19 1508–1517
E. Gao Y. Wang J.L. Alcorn C.R. Mendelson (2003) ArticleTitleTranscription factor USF2 is developmentally regulated in fetal lung and acts together with USF1 to induce SP-A gene expression Am. J. Physiol. Lung Cell. Mol. Physiol. 284 L1027–L1036
C. Grandori S.M. Cowley L.P. James R.N. Eisenman (2000) ArticleTitleThe Myc/Max/Mad network and the transcriptional control of cell behavior Annu. Rev. Cell. Dev. Biol. 16 653–699
B. Luscher (2001) ArticleTitleFunction and regulation of the transcription factors of the Myc/Max/Mad network Gene 277 1–14
S. Nasi R. Ciarapica R. Jucker J. Rosati L. Soucek (2001) ArticleTitleMaking decisions through Myc FEBS Lett. 490 153–162
Z.Q. Zhou P.J. Hurlin (2001) ArticleTitleThe interplay between Mad and Myc in proliferation and differentiation Trends Cell. Biol. 11 S10–S14
R.C. Sears J.R. Nevins (2002) ArticleTitleSignaling networks that link cell proliferation and cell fate J. Biol. Chem. 277 11617–11620
K. Hilger-Eversheim M. Moser H. Schorle R. Buettner (2000) ArticleTitleRegulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control Gene 260 1–12
J.M. Coulson C.E. Fiskerstrand P.J. Woll J.P. Quinn (1999) ArticleTitleE-box motifs within the human vasopressin gene promoter contribute to a major enhancer in small-cell lung cancer Biochem. J. 344 Pt 3 961–970
J.M. Coulson J.L. Edgson Z.V. Marshall-Jones R. Mulgrew J.P. Quinn P.J. Woll (2003) ArticleTitleUpstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box Biochem. J. 369 549–561
A.K. Gupta B.C. Kone (2002) ArticleTitleUSF-1 and USF-2 trans-repress IL-1β-induced iNOS transcription in mesangial cells Am. J. Physiol. Cell. Physiol. 283 C1065–C1072
T.W. Lee G.G. Chen H. Xu J.H. Yip E.C. Chak T.S. Mok A.P. Yim (2003) ArticleTitleDifferential expression of inducible nitric oxide synthase and peroxisome proliferator-activated receptor gamma in non-small cell lung carcinoma Eur. J. Cancer 39 1296–1301
L.R. Kisley B.S. Barrett A.K. Bauer L.D. Dwyer-Nield B. Barthel A.M. Meyer D.C. Thompson A.M. Malkinson (2002) ArticleTitleGenetic ablation of inducible nitric oxide synthase decreases mouse lung tumorigenesis Cancer Res. 62 6850–6856
S. Sharma B.P. Wilkinson P. Gao V.E. Steele (2002) ArticleTitleDifferential activity of NO synthase inhibitors as chemopreventive agents in a primary rat tracheal epithelial cell transformation system Neoplasia 4 332–336
W.C. Chang Y.C. Lee C.L. Liu J.D. Hsu H.C. Wang C.C. Chen C.J. Wang (2001) ArticleTitleIncreased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke Arch. Toxicol. 75 28–35
G. Garcon P. Gosset S. Garry T. Marez M.H. Hannothiaux P. Shirali (2001) ArticleTitlePulmonary induction of proinflammatory mediators following the rat exposure to benzo(a)pyrene-coated onto Fe2O3 particles Toxicol. Lett. 121 107–117
N. Wajapeyee K. Somasundaram (2003) ArticleTitleCell cycle arrest and apoptosis induction by activator protein 2 α (AP-2α) and the role of p53 and p21WAF1/CIP1 in AP-2α mediated growth inhibition J. Biol. Chem. 278 52093–52101
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Khattar, N.H., Lele, S.M. & Kaetzel, C.S. Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2. J Biomed Sci 12, 65–77 (2005). https://doi.org/10.1007/s11373-004-8185-5
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DOI: https://doi.org/10.1007/s11373-004-8185-5