Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin, β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis. 1. Introduction In canine species, spontaneous mammary tumours constitute the second most frequent neoplasia, surpassed only by skin tumours. When considering female dogs, mammary tumours represent the most common neoplasia, with malignant tumours accounting for up to 50% of cases [1]. Therefore, this disease represents a serious problem in worldwide veterinary practice and is a matter of concern for both oncologists and pathologists, which is ultimately reflected on the escalating number of studies in this research area. Furthermore, canine mammary tumours have attracted considerable attention over the years as possible animal models for human mammary neoplasia, based on their morphological and biological similarities [2–4]. Mammary tumours of the female dog are commonly associated with the development of distant metastases, which ultimately leads to morbidity and mortality. In the initial steps of this complex biological process, neoplastic cells lose intercellular adhesion in order to invade local tissues, and it is now evident that tumour invasion and progression may result from changes in cell adhesion systems. Based on sequence homology and structure, cell adhesion molecules are divided into the following families: cadherins, selectins, integrins, the immunoglobulin superfamily, and lymphocyte homing receptors, such as CD44 [5]. In this paper, we will discuss the findings on cadherin-mediated cell adhesion systems in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. 2. Overview of Cadherins Cadherins are calcium-dependent cell-cell adhesion molecules, believed to be essential in coordinating morphogenetic cell movements and in the maintenance of normal tissue architecture [6–8]. Over the last two decades, cadherin research has been focused on its
References
[1]
W. Misdorp, “Tumours of the mammary gland,” in Tumors in Domestic Animals, D. J. Meuten, Ed., pp. 575–606, Iowa State Press, Blackwell, Ames, Iowa, USA, 4th edition, 2002.
[2]
S. R. Gilbertson, I. D. Kurzman, and R. E. Zachrau, “Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs,” Veterinary Pathology, vol. 20, no. 2, pp. 127–142, 1983.
[3]
C. Khanna, K. Lindblad-Toh, D. Vail et al., “The dog as a cancer model,” Nature Biotechnology, vol. 24, no. 9, pp. 1065–1066, 2006.
[4]
P. N. Olson, “Using the canine genome to cure cancer and other diseases,” Theriogenology, vol. 68, no. 3, pp. 378–381, 2007.
[5]
N. Makrilia, A. Kollias, L. Manolopoulos, and K. Syrigos, “Cell adhesion molecules: role and clinical significance in cancer,” Cancer Investigation, vol. 27, no. 10, pp. 1023–1037, 2009.
[6]
M. Takeichi, “Cadherin cell adhesion receptors as a morphogenetic regulator,” Science, vol. 251, no. 5000, pp. 1451–1455, 1991.
[7]
B. M. Gumbiner, “Cell adhesion: the molecular basis of tissue architecture and morphogenesis,” Cell, vol. 84, no. 3, pp. 345–357, 1996.
[8]
D. M. Li and Y. M. Feng, “Signaling mechanism of cell adhesion molecules in breast cancer metastasis: potential therapeutic targets,” Breast Cancer Research and Treatment, vol. 128, no. 1, pp. 7–21, 2011.
[9]
A. Nose and M. Takeichi, “A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos,” Journal of Cell Biology, vol. 103, no. 6, pp. 2649–2658, 1986.
[10]
K. A. Knudsen and M. J. Wheelock, “Cadherins and the mammary gland,” Journal of Cellular Biochemistry, vol. 95, no. 3, pp. 488–496, 2005.
[11]
K. A. Knudsen, C. Frankowski, K. R. Johnson, and M. J. Wheelock, “A role for cadherins in cellular signaling and differentiation,” Journal of Cellular Biochemistry. Supplement, vol. 30-31, pp. 168–176, 1998.
[12]
Y. Shimoyama, T. Yoshida, M. Terada, Y. Shimosato, O. Abe, and S. Hirohashi, “Molecular cloning of a human Ca2+-dependent cell-cell adhesion molecule homologous to mouse placental cadherin: its low expression in human placental tissues,” Journal of Cell Biology, vol. 109, no. 4 I, pp. 1787–1794, 1989.
[13]
K. Hatta and M. Takeichi, “Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development,” Nature, vol. 320, no. 6061, pp. 447–449, 1986.
[14]
A. Nose, A. Nagafuchi, and M. Takeichi, “Isolation of placental cadherin cDNA: identification of a novel gene family of cell-cell adhesion molecules,” The EMBO Journal, vol. 6, no. 12, pp. 3655–3661, 1987.
[15]
S. Miyatani, K. Shimamura, M. Hatta et al., “Neural cadherin: role in selective cell-cell adhesion,” Science, vol. 245, no. 4918, pp. 631–635, 1989.
[16]
J. Paredes, A. L. Correia, A. S. Ribeiro, A. Albergaria, F. Milanezi, and F. C. Schmitt, “P-cadherin expression in breast cancer: a review,” Breast Cancer Research, vol. 9, no. 5, p. 214, 2007.
[17]
M. Ozawa, H. Barbault, and R. Kemler, “The cytoplasmic domain of the cell adhesion molecule uvomorulin assoicates with three independent proteins structurally related in different species,” The EMBO Journal, vol. 8, no. 6, pp. 1711–1717, 1989.
[18]
K. Vleminckx, L. Vakaet Jr., M. Mareel, W. Fiers, and F. Van Roy, “Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role,” Cell, vol. 66, no. 1, pp. 107–119, 1991.
[19]
P. D. McCrea, C. W. Turck, and B. Gumbiner, “A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin,” Science, vol. 254, no. 5036, pp. 1359–1361, 1991.
[20]
M. Peifer, P. D. McCrea, K. J. Green, E. Wieschaus, and B. M. Gumbiner, “The vertebrate adhesive junction proteins β-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties,” Journal of Cell Biology, vol. 118, no. 3, pp. 681–691, 1992.
[21]
J. Behrens, J. P. Von Kries, M. Kühl et al., “Functional interaction of β-catenin with the transcription factor LEF-1,” Nature, vol. 382, no. 6592, pp. 638–642, 1996.
[22]
O. Huber, R. Korn, J. McLaughlin, M. Ohsugi, B. G. Herrmann, and R. Kemler, “Nuclear localization of β-catenin by interaction with transcription factor LEF-1,” Mechanisms of Development, vol. 59, no. 1, pp. 3–10, 1996.
[23]
M. Molenaar, M. van de Wetering, M. Oosterwegel et al., “XTcf-3 transcription factor mediates β-catenin-induced axis formation in xenopus embryos,” Cell, vol. 86, no. 3, pp. 391–399, 1996.
[24]
M. van de Wetering, R. Cavallo, D. Dooijes et al., “Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF,” Cell, vol. 88, no. 6, pp. 789–799, 1997.
[25]
G. Berx and F. Van Roy, “The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression,” Breast Cancer Research, vol. 3, no. 5, pp. 289–293, 2001.
[26]
A. M. C. Brown, “Wnt signaling in breast cancer: have we come full circle?” Breast Cancer Research, vol. 3, no. 6, pp. 351–355, 2001.
[27]
N. Gavert and A. Ben-Ze'ev, “β-catenin signaling in biological control and cancer,” Journal of Cellular Biochemistry, vol. 102, no. 4, pp. 820–828, 2007.
[28]
T. M. Rowlands, I. V. Pechenkina, S. J. Hatsell, R. G. Pestell, and P. Cowin, “Dissecting the roles of β-catenin and cyclin D1 during mammary development and neoplasia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 20, pp. 11400–11405, 2003.
[29]
A. S. Yap, C. M. Niessen, and B. M. Gumbiner, “The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p ,” Journal of Cell Biology, vol. 141, no. 3, pp. 779–789, 1998.
[30]
T. Ohkubo and M. Ozawa, “p binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity,” The Journal of Biological Chemistry, vol. 274, no. 30, pp. 21409–21415, 1999.
[31]
P. Z. Anastasiadis, S. Y. Moon, M. A. Thoreson et al., “Inhibition of RhoA by p120 catenin,” Nature Cell Biology, vol. 2, no. 9, pp. 637–644, 2000.
[32]
M. J. Wheelock, A. P. Soler, and K. A. Knudsen, “Cadherin junctions in mammary tumors,” Journal of Mammary Gland Biology and Neoplasia, vol. 6, no. 3, pp. 275–285, 2001.
[33]
B. Restucci, S. Papparella, G. De Vico, and P. Maiolino, “E cadherin expression in normal and neoplastic canine mammary gland,” Journal of Comparative Pathology, vol. 116, no. 2, pp. 191–202, 1997.
[34]
G. Sarli, R. Preziosi, L. De Tolla, B. Brunetti, and C. Benazzi, “E-cadherin immunoreactivity in canine mammary tumors,” Journal of Veterinary Diagnostic Investigation, vol. 16, no. 6, pp. 542–547, 2004.
[35]
A. Gama, J. Paredes, F. G？rtner, A. Alves, and F. Schmitt, “Expression of E-cadherin, P-cadherin and β-catenin in canine malignant mammary tumours in relation to clinicopathological parameters, proliferation and survival,” Veterinary Journal, vol. 177, no. 1, pp. 45–53, 2008.
[36]
J. Palacios, N. Benito, A. Pizarro et al., “Anomalous expression of P-cadherin in breast carcinoma: correlation with E-cadherin expression and pathological features,” American Journal of Pathology, vol. 146, no. 3, pp. 605–612, 1995.
[37]
A. Gama, J. Paredes, M. F. Milanezi, J. S. Reis-Filho, F. Gartner, and F. C. Schmitt, “P-cadherin expression in canine lactating mammary gland,” Journal of Cellular Biochemistry, vol. 86, no. 3, pp. 420–421, 2002.
[38]
A. Gama, J. Paredes, A. Albergaria, F. Gartner, and F. Schmitt, “P-cadherin expression in canine mammary tissues,” Journal of Comparative Pathology, vol. 130, no. 1, pp. 13–20, 2004.
[39]
A. P. Soler, J. Russo, I. H. Russo, and K. A. Knudsen E, “Soluble fragment of P-cadherin adhesion protein found in human milk,” Journal of Cellular Biochemistry, vol. 85, no. 1, pp. 180–184, 2002.
[40]
A. L. Reis, J. Carvalheira, F. C. Schmitt, and F. G？rtner, “Immunohistochemical study of the expression of E-cadherin in canine mammary tumours,” Veterinary Record, vol. 152, no. 20, pp. 621–624, 2003.
[41]
B. Brunetti, G. Sarli, R. Preziosi, I. Monari, and C. Benazzi, “E-cadherin and β-catenin reduction influence invasion but not proliferation and survival in canine malignant mammary tumors,” Veterinary Pathology, vol. 42, no. 6, pp. 781–787, 2005.
[42]
A. J. F. Matos, C. Lopes, J. Carvalheira, M. Santos, G. R. Rutteman, and F. G？rtner, “E-cadherin expression in canine malignant mammary tumours: relationship to other clinico-pathological variables,” Journal of Comparative Pathology, vol. 134, no. 2-3, pp. 182–189, 2006.
[43]
A. J. F. de Matos, C. C. C. Lopes, A. M. R. Faustino, J. G. V. Carvalheira, G. R. Rutteman, and M. D. F. R. M. G？rtner, “E-cadherin, β-catenin, invasion and lymph node metastases in canine malignant mammary tumours,” Acta Pathologica, Microbiologica et Immunologica, vol. 115, no. 4, pp. 327–334, 2007.
[44]
M. Nowak, J. A. Madej, and P. Dziegiel, “Expression of E-cadherin, β-catenin and Ki-67 antigen and their reciprocal relationships in mammary adenocarcinomas in bitches,” Folia Histochemica et Cytobiologica, vol. 45, no. 3, pp. 233–238, 2007.
[45]
A. Rodo and E. Malicka, “E-cadherin immimohistochemical expression in mammary gland neoplasms in bitches,” Polish Journal of Veterinary Sciences, vol. 11, no. 1, pp. 47–54, 2008.
[46]
B. P. L. Wijnhoven, W. N. M. Dinjens, and M. Pignatelli, “E-cadherin-catenin cell-cell adhesion complex and human cancer,” British Journal of Surgery, vol. 87, no. 8, pp. 992–1005, 2000.
[47]
U. H. Frixen, J. Behrens, M. Sachs et al., “E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells,” Journal of Cell Biology, vol. 113, no. 1, pp. 173–185, 1991.
[48]
A. K. Peri, P. Wilgenbus, U. Dahl, H. Semb, and G. Christofori, “A causal role for E-cadherin in the transition from adenoma to carcinoma,” Nature, vol. 392, no. 6672, pp. 190–193, 1998.
[49]
C. B. J. Vos, A. M. Cleton-Jansen, G. Berx et al., “E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumerigenesis,” British Journal of Cancer, vol. 76, no. 9, pp. 1131–1133, 1997.
[50]
C. Gamallo, J. Palacios, A. Suarez et al., “Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma,” American Journal of Pathology, vol. 142, no. 4, pp. 987–993, 1993.
[51]
H. Oka, H. Shiozaki, K. Kobayashi et al., “Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis,” Cancer Research, vol. 53, no. 7, pp. 1696–1701, 1993.
[52]
S. M. Siitonen, J. T. Kononen, H. J. Helin, I. S. Rantala, K. A. Holli, and J. J. Isola, “Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer,” American Journal of Clinical Pathology, vol. 105, no. 4, pp. 394–402, 1996.
[53]
I. K. Bukholm, J. M. Nesland, R. Karesen, U. Jacobsen, and A. L. Borresen-Dale, “E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma,” Journal of Pathology, vol. 185, pp. 262–266, 1998.
[54]
R. Heimann, F. Lan, R. McBride, and S. Hellman, “Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin,” Cancer Research, vol. 60, no. 2, pp. 298–304, 2000.
[55]
M. Madhavan, P. Srinivas, E. Abraham et al., “Cadherins as predictive markers of nodal metastasis in breast cancer,” Modern Pathology, vol. 14, no. 5, pp. 423–427, 2001.
[56]
R. Yoshida, N. Kimura, Y. Harada, and N. Ohuchi, “The loss of E-cadherin, alpha- and beta-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer,” International Journal of Oncology, vol. 18, no. 3, pp. 513–520, 2001.
[57]
G. Berx, A. M. Cleton-Jansen, F. Nollet et al., “E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers,” The EMBO Journal, vol. 14, no. 24, pp. 6107–6115, 1995.
[58]
L. Ressel, F. Millanta, and A. Poli, “Canine invasive lobular carcinoma of the mammary gland: morphological and immunohistochemical characterizations of three cases,” Journal of Comparative Pathology, vol. 144, no. 4, pp. 303–307, 2011.
[59]
M. Nowak, J. A. Madej, M. Podhorska-Okolow, and P. Dziegiel, “Expression of extracellular matrix metalloproteinase (MMP-9), E-cadherin and proliferation-associated antigen Ki-67 and their reciprocal correlation in canine mammary adenocarcinomas,” In Vivo, vol. 22, no. 4, pp. 463–470, 2008.
[60]
A. Kovács, J. Dhillon, and R. A. Walker, “Expression of P-cadherin, but not E-cadherin or N-cadherin, relates to pathological and functional differentiation of breast carcinomas,” Journal of Clinical Pathology, vol. 56, no. 6, pp. 318–322, 2003.
[61]
C. E. Gillett, D. W. Miles, K. Ryder et al., “Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast,” Journal of Pathology, vol. 193, no. 4, pp. 433–441, 2001.
[62]
E. M. Howard, S. K. Lau, R. H. Lyles, G. G. Birdsong, J. N. Umbreit, and R. Kochhar, “Expression of E-cadherin in high-risk breast cancer,” Journal of Cancer Research and Clinical Oncology, vol. 131, no. 1, pp. 14–18, 2005.
[63]
N. Spieker, M. Mareel, E. A. Bruyneel, and H. Nederbragt, “E-cadherin expression and in vitro invasion of canine mammary tumor cells,” European Journal of Cell Biology, vol. 68, no. 4, pp. 427–436, 1995.
[64]
B. Brunetti, G. Sarli, R. Preziosi, S. Leprotti, and C. Benazzi, “E-cadherin expression in canine mammary carcinomas with regional lymph node metastases,” Journal of Veterinary Medicine A, vol. 50, no. 10, pp. 496–500, 2003.
[65]
I. K. Bukholm and J. M. Nesland, “Re-expression of E-cadherin, α-catenin and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients,” ,Journal of Pathology, vol. 190, pp. 15–19, 2000.
[66]
S. S. Pinho, H. Osório, M. Nita-Lazar et al., “Role of E-cadherin N-glycosylation profile in a mammary tumor model,” Biochemical and Biophysical Research Communications, vol. 379, no. 4, pp. 1091–1096, 2009.
[67]
M. A. Gonzalez, S. E. Pinder, P. M. Wencyk, et al., “An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer,” Journal of Pathology, vol. 187, pp. 523–529, 1999.
[68]
A. Soler, K. A. Knudsen, H. Salazar, A. C. Han, and A. A. Keshgegian, “P-cadherin expression in breast carcinoma indicates poor survival,” Cancer, vol. 86, pp. 1263–1272, 1999.
[69]
M. Dolled-Filhart, A. McCabe, J. Giltnane, M. Cregger, R. L. Camp, and D. L. Rimm, “Quantitative in situ analysis of β-catenin expression in breast cancer shows decreased expression is associated with poor outcome,” Cancer Research, vol. 66, no. 10, pp. 5487–5494, 2006.
[70]
B. E. Gould Rothberg and M. B. Bracken, “E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis,” Breast Cancer Research and Treatment, vol. 100, no. 2, pp. 139–148, 2006.
[71]
D. Park, R. K？resen, U. Axcrona, T. Noren, and T. Sauer, “Expression pattern of adhesion molecules (E-cadherin, α-, β-, γ-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis,” Acta Pathologica, Microbiologica et Immunologica, vol. 115, no. 1, pp. 52–65, 2007.
[72]
C. G. Kleer, K. L. van Golen, T. Braun, and S. D. Merajver, “Persistent E-cadherin expression in inflammatory breast cancer,” Modern Pathology, vol. 14, no. 5, pp. 458–464, 2001.
[73]
E. Charafe-Jauffret, C. Tarpin, V. J. Bardou et al., “Immunophenotypic analysis of inflammatory breast cancers: identification of an ‘inflammatory signature’,” Journal of Pathology, vol. 202, no. 3, pp. 265–273, 2004.
[74]
C. Gamallo, G. Moreno-Bueno, D. Sarrió, F. Calero, D. Hardisson, and J. Palacios, “The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma,” Modern Pathology, vol. 14, no. 7, pp. 650–654, 2001.
[75]
J. Paredes, F. Milanezi, J. S. Reis-Filho, D. Leit？o, D. Athanazio, and F. Schmitt, “Aberrant P-cadherin expression: is it associated with estrogen-independent growth in breast cancer?” Pathology Research and Practice, vol. 198, no. 12, pp. 795–801, 2002.
[76]
J. B. Arnes, J. S. Brunet, I. Stefansson et al., “Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer,” Clinical Cancer Research, vol. 11, no. 11, pp. 4003–4011, 2005.
[77]
J. Paredes, A. Albergaria, J. T. Oliveira, C. Jeronimo, F. Milanezi, and F. C. Schmitt, “P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation,” Clinical Cancer Research, vol. 11, no. 16, pp. 5869–5877, 2005.
[78]
G. Turashvili, S. E. McKinney, O. Goktepe et al., “P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer,” Modern Pathology, vol. 24, no. 1, pp. 64–81, 2011.
[79]
A. C. Han, A. P. Soler, K. A. Knudsen, and H. Salazar, “Distinct cadherin profiles in special variant carcinomas and other tumors of the breast,” Human Pathology, vol. 30, no. 9, pp. 1035–1039, 1999.
[80]
J. S. Reis-Filho, F. Milanezi, J. Paredes et al., “Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast,” Applied Immunohistochemistry and Molecular Morphology, vol. 11, no. 1, pp. 1–8, 2003.
[81]
C. M. Perou, T. S？rile, M. B. Eisen et al., “Molecular portraits of human breast tumours,” Nature, vol. 406, no. 6797, pp. 747–752, 2000.
[82]
T. S？rlie, C. M. Perou, R. Tibshirani et al., “Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10869–10874, 2001.
[83]
T. S？rlie, R. Tibshirani, J. Parker et al., “Repeated observation of breast tumor subtypes in independent gene expression data sets,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 14, pp. 8418–8423, 2003.
[84]
C. Sotiriou, S. Y. Neo, L. M. McShane et al., “Breast cancer classification and prognosis based on gene expression profiles from a population-based study,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 18, pp. 10393–10398, 2003.
[85]
A. Prat, J. S. Parker, O. Karginova et al., “Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer,” Breast Cancer Research, vol. 12, no. 5, article R68, 2010.
[86]
T. O. Nielsen, F. D. Hsu, K. Jensen et al., “Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma,” Clinical Cancer Research, vol. 10, no. 16, pp. 5367–5374, 2004.
[87]
I. Matos, R. Dufloth, M. Alvarenga, L. C. Zeferino, and F. Schmitt, “p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas,” Virchows Archiv, vol. 447, no. 4, pp. 688–694, 2005.
[88]
E. A. Rakha, M. E. El-Sayed, J. Reis-Filho, and I. O. Ellis, “Patho-biological aspects of basal-like breast cancer,” Breast Cancer Research and Treatment, vol. 113, no. 3, pp. 411–422, 2009.
[89]
B. Sousa, J. Paredes, F. Milanezi et al., “P-cadherin, Vimentin and CK14 for identification of basal-like phenotype in breast carcinomas: an immunohistochemical study,” Histology and Histopathology, vol. 25, no. 8, pp. 963–974, 2010.
[90]
A. Gama, A. Alves, and F. Schmitt, “Identification of molecular phenotypes in canine mammary carcinomas with clinical implications: application of the human classification,” Virchows Archiv, vol. 453, no. 2, pp. 123–132, 2008.
[91]
J. C. Paredes, M. F. G. Milanezi, J. S. Reis-Filho, D. R. A. Leit？o, D. A. Athanazio, and F. C. De Landér Schmitt, “Correlation between P-cadherin and estrogen receptor expression in breast cancer,” Jornal Brasileiro de Patologia e Medicina Laboratorial, vol. 38, no. 4, pp. 307–313, 2002.
[92]
J. Paredes, C. Stove, V. Stove et al., “P-cadherin is up-regulated by the antiestrogen ICI 182,780 and promotes invasion of human breast cancer cells,” Cancer Research, vol. 64, no. 22, pp. 8309–8317, 2004.
[93]
A. Albergaria, A. S. Ribeiro, S. Pinho et al., “ICI 182,780 induces P-cadherin overexpression in breast cancer cells through chromatin remodelling at the promoter level: a role for C/EBPβ in CDH3 gene activation,” Human Molecular Genetics, vol. 19, no. 13, pp. 2554–2566, 2010.
[94]
A. S. Ribeiro, A. Albergaria, B. Sousa et al., “Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells,” Oncogene, vol. 29, no. 3, pp. 392–402, 2010.
[95]
K. Taniuchi, H. Nakagawa, M. Hosokawa et al., “Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating Rho-family GTPases,” Cancer Research, vol. 65, no. 8, pp. 3092–3099, 2005.
[96]
C. C. Zhang, Z. Yan, Q. Zhang et al., “PF-03732010: a fully human monoclonal antibody against P-cadherin with antitumor and antimetastatic activity,” Clinical Cancer Research, vol. 16, no. 21, pp. 5177–5188, 2010.
