The presence of parathyroid hormone-related protein (PTHrP) in the apocrine adenocarcinoma tumor line (CAC-8) derived from a hypercalcemic dog was demonstrated by western and northern blot analyses. Western blots of CAC-8 tumor extracts revealed a major protein with a molecular weight of approximately 18,000 daltons that cross-reacted with antiserum to human PTHrP. Northern blots demonstrated multiple-sized messenger RNA transcripts in CAC-8 that hybridized to a full-length cDNA probe to human PTHrP. Adenocarcinomas derived from apocrine glands of the anal sac also were stained immunohistochemically for antigens that cross-react with antiserum to human PTHrP. The tumor line (CAC-8) maintained in nude mice stained positively for PTHrP in 13 of 24 tumors. Three of ten apocrine adenocarcinomas from dogs with hypercalcemia stained for PTHrP, whereas zero of ten tumors were positive from normocalcemic dogs. Normal canine epidermal keratinocytes and areas of squamous metaplasia in a perianal gland carcinoma also were positive for PTHrP. These data demonstrated that canine tissues contained a homologue to human PTHrP that likely is important in the pathogenesis of humoral hypercalcemia of malignancy.
BroadusAEManginMInsognaKLWeirECBurtisWJStewartAF:
Humoral hypercalcemia of malignancy. Identification of a novel parathyroid hormone-like peptide.
New Engl J Med319:
556–563,
1988
3.
DanksJEbelingPHaymanJChouSMoseleyJDunlopJKempBMartinT:
Parathyroid hormone-related protein: immunohistochemical localization in cancers and in normal skin.
J Bone Min Res4:
273–278,
1989
4.
DeftosLGazdarAIkedaKBroadusA:
The parathyroid hormone-related protein associated with malignancy is secreted by neuroendocrine tumors.
Mol Endo3:
503–508,
1989
HaymanJADanksJAEbelingPRMoseleyJMKempBEMartinTJ:
Expression of parathyroid hormone related protein in normal skin and in tumors of skin and skin appendages.
J Pathol158:
293–296,
1989
7.
IkedaKManginMDreyerBEWebbACPosillicoJTStewartAFBanderNHWeirECInsognaKLBroadusAE:
Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.
J Clin Invest81:
2010–2014,
1988
8.
IkedaKWeirEManginMDanniesPKinderBDeftosLBrownEBroadusA:
Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas.
Mol Endo2:
1230–1236,
1988
9.
KempBEMoseleyJMRoddaCPEbelingPRWettenhallREHStapletonDDiefenbach-JaggerHUreFMichelangeliVPSimmonsHARaiszLGMartinTJ:
Parathyroid hormone-related protein of malignancy: active synthetic fragments.
Science238:
1568–1570,
1987
10.
KukrejaSCShevrinDHWimbicusSAEbelingPRDanksJARoddaCPWoodWIMartinTJ:
Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy-associated hypercalcemia due to human tumors.
J Clin Invest82:
1798–1802,
1988
11.
ManginMIkedaKDreyerBBroadusA:
Isolation and characterization of the human parathyroid hormonelike peptide gene.
Proc Natl Acad Sci USA86:
2408–2412,
1989
12.
ManginMIkedaKDreyerBEMilstoneLBroadusAE:
Two distinct tumor-derived, parathyroid hormonelike peptides result from alternative ribonucleic acid splicing.
Mol Endo2:
1049–1055,
1988
13.
ManginMWebbACDreyerBEPosillicoJTIkedaKWeirECStewartAFBanderNHMilstoneLBartonDEFranckeUBroadusAE:
Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy.
Proc Natl Acad Sci USA85:
597–601,
1988
14.
MerrymanJIRosolTJBrooksCLCapenCC:
Separation of parathyroid hormone-like activity from transforming growth factor alpha and beta in the canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.
Endocrinology124:
2456–2563,
1989
15.
MeutenDJCooperBJCapenCCChewDJKocibaGJ:
Hypercalcemia associated with an adenocarcinoma derived from the apocrine glands of the anal sac.
Vet Pathol18:
454–471,
1981
16.
MeutenDJSegreGVCapenCCKocibaGJVoekelEFLevineLTashjianAHChewDJNagodeLA:
Hypercalcemia in dogs with adenocarcinoma derived from apocrine glands of the anal sac: biochemical and histomorphometric investigations.
Lab Invest48:
428–435,
1983
17.
MoseleyJMKubotaMDiefenbach-JaggerHWettenhallREHKempBESuvaLJRoddaCPEbelingPRHudsonPJZajacJDMartinTJ:
Parathyroid hormone-related protein purified from a human lung cancer cell line.
Proc Natl Acad Sci USA84:
5048–5052,
1987
18.
MundyGR:
Hypercalcemia of malignancy revisited.
J Clin Invest82:
1–6,
1988
19.
RobertsABLambLCNewtonDLSpornMBDeLarcoJETodaroGJ:
Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction.
Cell Biol77:
3494–3498,
1980
20.
RoddaCPKubotaMHeathJAEbelingPRMoseleyJMCareADCapleIWMartinTJ:
Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcemia of malignancy.
J Endocrinol117:
261–271,
1988
21.
RosolTJCapenCC:
Inhibition of in vitro bone resorption by a parathyroid hormone receptor antagonist in the canine adenocarcinoma model of humoral hypercalcemia of malignancy.
Endocrinology122:
2098–2102,
1988
22.
RosolTJCapenCC:
Pathogenesis of humoral hypercalcemia of malignancy.
Domes An Endocrinol5:
1–21,
1988
23.
RosolTJCapenCCBrooksCL:
Bone and kidney adenylate cyclase-stimulating activity produced by a hypercalcemic canine adenocarcinoma line (CAC-8) maintained in nude mice.
Cancer Res47:
690–695,
1987
24.
RosolTJCapenCCHorstRL:
Effects of infusion of human parathyroid hormone-related protein (1-40) in nude mice: histomorphometric and biochemical investigations.
J Bone Min Res3:
699–706,
1988
25.
RosolTJCapenCCMinkinC:
In vitro bone resorption activity produced by a hypercalcemic adenocarcinoma tumor line (CAC-8) in nude mice.
Calcif Tissue Int39:
334–341,
1986
26.
RosolTJCapenCCWeisbrodeSEHorstRL:
Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac.
Lab Invest54:
679–688,
1986
27.
SternbergerLAHardyPHCuculisJJMeyerHG:
The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorse-radish peroxidase) and its use in identification of spirochetes.
J Histochem Cytochem18:
315–333,
1970
28.
SuvaLJMatherKAGillespieMTWebbGCNgKWWinslowGAWoodWIMartinTJHudsonPJ:
Structure of the 5′ flanking region of the gene encoding human parathryoid-hormone-related protein (PTHrP).
Gene77:
95–105,
1989
29.
SuvaLJWinslowGAWettenhallREHHammondsRGMoseleyJMDiefenbach-JaggerHRoddaCPKempBERodriquezHChenEYHudsonPJMartinTJWoodWI:
A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression.
Science237:
893–896,
1987
30.
ThiedeMRodanG:
Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue.
Science242:
278–280,
1988
31.
ThiedeMAStrewlerGJNissensonRARosenblattMRodanGA:
Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single copy gene.
Proc Natl Acad Sci USA85:
4605–4609,
1988
32.
WeirECBurtisWJMorrisCABradyTGInsognaKL:
Isolation of 16,000-dalton parathyroid hormonelike proteins from two animal tumors causing humoral hypercalcemia of malignancy.
Endocrinology123:
2744–2751,
1988
33.
YasudaTBanvilleDHendyGNGoltzmanD:
Characterization of the human parathyroid hormone-like peptide gene: functional and evolutionary aspects.
J Biol Chem264:
7720–7725,
1989
34.
YasudaTBanvilleDRabbaniSHendyGGoltzmanD:
Rat parathyroid hormone-like peptide: comparison with the human homologue and expression in malignant and normal tissue.
Mol Endo3:
518–525,
1989
