期刊论文详细信息
BMC Veterinary Research
Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas
Iris M Reichler3  Franco Guscetti1  Alois Boos2  Carla Rohrer Bley4  Mariusz P Kowalewski2  Stefanie K Feldmann3  Erika Michel3 
[1] Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland;Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland;Clinic for Reproductive Medicine, Unit of Small Animal Reproduction, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland;Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland
关键词: Prolactin receptor;    Prolactin;    Mammary tumor;    Canine;    Dog;   
Others  :  1119815
DOI  :  10.1186/1746-6148-8-72
 received in 2011-08-16, accepted in 2012-05-14,  发布年份 2012
PDF
【 摘 要 】

Background

Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas.

Results

The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells.

Conclusions

Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding.

【 授权许可】

   
2012 Michel et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150208130705323.pdf 1421KB PDF download
Figure 2. 281KB Image download
Figure 1. 17KB Image download
【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】
  • [1]Freeman ME, Kanyicska B, Lerant A, Nagy G: Prolactin: structure, function, and regulation of secretion. Physiol Rev 2000, 80:1523-1631.
  • [2]Joechle W: Prolactin in canine and feline reproduction. Reprod Domest Anim 1997, 32:183-193.
  • [3]Kooistra HS, Okkens AC: Secretion of prolactin and growth hormone in relation to ovarian activity in the dog. Reprod Dom Anim 2001, 36:115-119.
  • [4]Verstegen-Onclin K, Verstegen J: Endocrinology of pregnancy in the dog: a review. Theriogenology 2008, 70:291-299.
  • [5]Vonderhaar BK: Prolactin: the forgotten hormone of human breast cancer. Pharmacol Ther 1998, 79:169-178.
  • [6]Harvey PW, Everett DJ, Springall CJ: Hyperprolactinaemia as an adverse effect in regulatory and clinical toxicology: role in breast and prostate cancer. Hum Exp Toxicol 2006, 25:395-404.
  • [7]Bernichtein S, Touraine P, Goffin V: New concepts in prolactin biology. J Endocrinol 2010, 206:1-11.
  • [8]Fernandez I, Touraine P, Goffin V: Prolactin and human tumourogenesis. J Neuroendocrinol 2010, 22:771-777.
  • [9]Clevenger CV, Furth PA, Hankinson SE, Schuler LA: The role of prolactin in mammary carcinoma. Endocr Rev 2003, 24:1-27.
  • [10]Ormandy CJ, Hall RE, Manning DL, Robertson JF, Blamey RW, Kelly PA, Nicholson RI, Sutherland RL: Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer. J Clin Endocrinol Metab 1997, 82:3692-3699.
  • [11]Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV: Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 1997, 138:5555-5560.
  • [12]Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F, Malet C, Nicolas A, Trivin C, Postel-Vinay MC, Kuttenn F, Kelly PA: Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab 1998, 83:667-674.
  • [13]Gill S, Peston D, Vonderhaar BK, Shousha S: Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 2001, 54:956-960.
  • [14]Meng J, Tsai-Morris CH, Dufau ML: Human prolactin receptor variants in breast cancer: low ratio of short forms to the long-form human prolactin receptor associated with mammary carcinoma. Cancer Res 2004, 64:5677-5682.
  • [15]Ferreira M, Mesquita M, Quaresma M, Andre S: Prolactin receptor expression in gynaecomastia and male breast carcinoma. Histopathology 2008, 53:56-61.
  • [16]Clevenger CV, Chang WP, Ngo W, Pasha TL, Montone KT, Tomaszewski JE: Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop. Am J Pathol 1995, 146:695-705.
  • [17]Mertani HC, Garcia-Caballero T, Lambert A, Gerard F, Palayer C, Boutin JM, Vonderhaar BK, Waters MJ, Lobie PE, Morel G: Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int J Cancer 1998, 79:202-211.
  • [18]Peirce SK, Chen WY, Chen WY: Quantification of prolactin receptor mRNA in multiple human tissues and cancer cell lines by real time RT-PCR. J Endocrinol 2001, 171:R1-R4.
  • [19]Vail DM, MacEwen EG: Spontaneously occurring tumors of companion animals as models for human cancer. Cancer Invest 2000, 18:781-792.
  • [20]Mellin A: Die Mammatumorerkrankung der Hündin und ihre Eignung als biologisches Modell für die Frau: Histologie, Malignitätsgrad, Immunhistochemie und Krankheitsverlauf. Inaugural-Dissertation, Tierärztliche Hochschule Hannover 2004,  : .
  • [21]Paoloni M, Khanna C: Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 2008, 8:147-156.
  • [22]Sorenmo KU, Kristiansen VM, Cofone MA, Shofer FS, Breen AM, Langeland M, Mongil CM, Grondahl AM, Teige J, Goldschmidt MH: Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence. Vet Comp Oncol 2009, 7:162-172.
  • [23]Klopfleisch R, von Euler H, Sarli G, Pinho SS, Gärtner F, Gruber AD: Molecular carcinogenesis of canine mammary tumors: news from an old disease. Vet Pathol 2011, 48:98-116.
  • [24]Rivera P, von Euler H: Molecular biological aspects on canine and human mammary tumors. Vet Pathol 2011, 48:132-146.
  • [25]Sorenmo K: Canine mammary gland tumors. Vet Clin North Am Small Anim Pract 2003, 33:573-596.
  • [26]Brodey RS, Goldschmidt MH, Roszel JR: Canine mammary neoplasms. J Am Anim Hosp Assoc 1983, 19:61-90.
  • [27]Dorn CR, Taylor DO, Schneider R, Hibbard HH, Klauber MR: Survey of animal neoplasms in Alameda and Contra Costa Counties, California. II. Cancer morbidity in dogs and cats from Alameda County. J Natl Cancer Inst 1968, 40:307-318.
  • [28]Schneider R, Dorn CR, Taylor DO: Factors influencing canine mammary cancer development and postsurgical survival. J Natl Cancer Inst 1969, 43:1249-1261.
  • [29]Sorenmo KU, Rasotto R, Zappulli V, Goldschmidt MH: Development, anatomy, histology, lymphatic drainage, clinical features, and cell differentiation markers of canine mammary gland neoplasms. Vet Pathol 2011, 48:85-97.
  • [30]Taylor GN, Shabestari L, Williams J, Mays CW, Angus W, McFarland S: Mammary neoplasia in a closed beagle colony. Cancer Res 1976, 36:2740-2743.
  • [31]Perez Alenza MD, Pena L, del Castillo N, Nieto AI: Factors influencing the incidence and prognosis of canine mammary tumours. J Small Anim Pract 2000, 41:287-291.
  • [32]Hamilton JM, Knight PJ, Beevers J, Else RW: Serum prolactin concentrations in canine mammary cancer. Vet Rec 1978, 102:127-128.
  • [33]El Etreby MF, Muller-Peddinghaus R, Bhargava AS, El Bab MR, Graf KJ, Trautwein G: The role of the pituitary gland in spontaneous canine mammary tumorigenesis. Vet Pathol 1980, 17:2-16.
  • [34]Rutteman GR, Willekes-Koolschijn N, Bevers MM, Van der Gugten AA, Misdorp W: Prolactin binding in benign and malignant mammary tissue of female dogs. Anticancer Res 1986, 6:829-835.
  • [35]van Garderen E, Swennenhuis JF, Hellmen E, Schalken JA: Growth hormone induces tyrosyl phosphorylation of the transcription factors Stat5a and Stat5b in CMT-U335 canine mammary tumor cells. Domest Anim Endocrinol 2001, 20:123-135.
  • [36]Queiroga FL, Perez-Alenza MD, Silvan G, Pena L, Lopes C, Illera JC: Role of steroid hormones and prolactin in canine mammary cancer. J Steroid Biochem Mol Biol 2005, 94:181-187.
  • [37]Kowalewski MP, Mason JI, Howie AF, Morley SD, Schuler G, Hoffmann B: Characterization of the canine 3beta-hydroxysteroid dehydrogenase and its expression in the corpus luteum during diestrus. J Steroid Biochem Mol Biol 2006, 101:254-262.
  • [38]Kowalewski MP, Schuler G, Taubert A, Engel E, Hoffmann B: Expression of cyclooxygenase 1 and 2 in the canine corpus luteum during diestrus. Theriogenology 2006, 66:1423-1430.
  • [39]Kowalewski MP, Michel E, Gram A, Boos A, Guscetti F, Hoffmann B, Aslan S, Reichler I: Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus and in luteal and placental tissues during pregnancy and at normal and induced parturition. Reprod Biol Endocrinol 2011, 9:109. BioMed Central Full Text
  • [40]Galsgaard ED, Rasmussen BB, Folkesson CG, Rasmussen LM, Berchtold MW, Christensen L, Panina S: Re-evaluation of the prolactin receptor expression in human breast cancer. J Endocrinol 2009, 201:115-128.
  • [41]Bhatavdekar JM, Patel DD, Shah NG, Vora HH, Suthar TP, Ghosh N, Chikhlikar PR, Trivedi TI: Prolactin as a local growth promoter in patients with breast cancer: GCRI experience. Eur J Surg Oncol 2000, 26:540-547.
  • [42]Ballestar E, Paz MF, Valle L, Wei S, Fraga MF, Espada J, Cigudosa JC, Huang TH, Esteller M: Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J 2003, 22:6335-6345.
  • [43]Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT, Rui H: Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 2005, 24:746-760.
  • [44]Sultan AS, Brim H, Sherif ZA: Co-overexpression of Janus kinase 2 and signal transducer and activator of transcription 5a promotes differentiation of mammary cancer cells through reversal of epithelial-mesenchymal transition. Cancer Sci 2008, 99:272-279.
  • [45]Nouhi Z, Chughtai N, Hartley S, Cocolakis E, Lebrun JJ, Ali S: Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells. Cancer Res 2006, 66:1824-1832.
  • [46]Wagner KU, Rui H: Jak2/Stat5 signalling in mammogenesis, breast cancer initiation and progression. J Mammary Gland Biol Neoplasia 2008, 13:93-103.
  • [47]Tran TH, Utama FE, Lin J, Yang N, Sjolund AB, Ryder A, Johnson KJ, Neilson LM, Liu C, Brill KL, Rosenberg AL, Witkiewicz AK, Rui H: Prolactin inhibits BCL6 expression in breast cancer through a Stat5a-dependent mechanism. Cancer Res 2010, 70:1711-1721.
  • [48]McHale K, Tomaszewski JE, Puthiyaveettil R, Livolsi VA, Clevenger CV: Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma. Mod Pathol 2008, 21:565-571.
  • [49]Plotnikov A, Varghese B, Tran TH, Liu C, Rui H, Fuchs SY: Impaired turnover of prolactin receptor contributes to transformation of human breast cells. Cancer Res 2009, 69:3165-3172.
  • [50]Rehm S, Stanislaus DJ, Williams AM: Estrous cycle-dependent histology and review of sex steroid receptor expression in dog reproductive tissues and mammary gland and associated hormone levels. Birth Defects Res B Dev Reprod Toxicol 2007, 80:233-245.
  • [51]Trott JF, Horigan KC, Gloviczki JM, Costa KM, Freking BA, Farmer C, Hayashi K, Spencer T, Morabito JE, Hovey RC: Tissue-specific regulation of porcine prolactin receptor expression by estrogen, progesterone, and prolactin. J Endocrinol 2009, 202:153-166.
  • [52]Rutteman GR, Bevers MM, Misdorp W, Van den Brom WE: Anterior pituitary function in female dogs with mammary tumors: II. Prolactin. Anticancer Res 1989, 9:241-245.
  • [53]Kreeger TJ, Seal US: Circannual prolactin rhythm in intact dogs housed outdoors. Chronobiologia 1992, 19:1-8.
  • [54]Kooistra HS: Adenohypophyseal Function in Healthy Dogs and in Dogs with Pituitary Disease. Thesis, Utrecht University; 2000.
  • [55]Gobello C, Bolognani F, de la Sota RL, Goya RG: Twenty-four-hour profiles of serum prolactin and luteinizing hormone in anoestrous crossbred bitches. Reprod Domest Anim 2001, 36:41-45.
  • [56]Corrada Y, Castex G, Sosa Y, Gobello C: Secretory patterns of prolactin in dogs: circannual and ultradian rhythms. Reprod Domest Anim 2003, 38:219-223.
  • [57]Martin LJM, Siliart B, Dumon HJW, Nguyen P: Spontaneous hormonal variations in male cats following gonadectomy. J Feline Med Surg 2006, 8:309-314.
  • [58]Corrada Y, Rimoldi I, Arreseigor S, Marecco G, Gobello C: Prolactin reference range and pulsatility in male dogs. Theriogenology 2006, 66:1599-1602.
  • [59]Urhausen C, Seefeldt A, Eschricht FM, Koch A, Hoppen HO, Beyerbach M, Mohrke C, Dieleman SJ, Gunzel-Apel AR: Concentrations of prolactin, LH, testosterone, TSH and thyroxine in normospermic dogs of different breeds. Reprod Domest Anim 2009, 44(Suppl 2):279-282.
  文献评价指标  
  下载次数:12次 浏览次数:5次