Mucins in the pathogenesis of breast cancer: Implications in diagnosis, prognosis and therapy

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1815, Issue 2, 2011, Pages 224-240

  Mukhopadhyay, Partha ^a   Chakraborty, Subhankar ^a   Ponnusamy, Moorthy P ^a   Lakshmanan, Imayavaramban ^a   Jain, Maneesh ^a   Batra, Surinder K ^a,b  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Apoptosis; Breast cancer; Cancer; Cell survival; MUC1 (DF3); MUC16 (CA125); MUC4; Mucins; Polymorphic epithelial mucins

Indexed keywords

CA 15-3 ANTIGEN; CELL ADHESION MOLECULE; GROWTH FACTOR RECEPTOR; MICRORNA; MUCIN; MUCIN 1; MUCIN 16; MUCIN 2; MUCIN 3; MUCIN 4; MUCIN 5AC; MUCIN 5B; MUCIN 6; MUCIN 7; TRASTUZUMAB; TUMOR MARKER; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; BREAST CARCINOGENESIS; BREAST TUMOR; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER INVASION; CANCER STEM CELL; CANCER TISSUE; COMPLEX FORMATION; DRUG TARGETING; HISTOPATHOLOGY; HUMAN; MOLECULAR INTERACTION; MOLECULAR WEIGHT; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; PROTEIN STRUCTURE; REVIEW; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; TUMOR EMBOLISM;

ANIMALS; BREAST NEOPLASMS; DISEASE PROGRESSION; FEMALE; HUMANS; MUCINS; PROGNOSIS;

EID: 79951583142     PISSN: 0304419X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbcan.2011.01.001     Document Type: Review

References (137)

1. Jemal A., Siegel R., Xu J., Ward E. Cancer Statistics, 2010. CA Cancer J. Clin. 2010.
2. Simpson P.T., Reis-Filho J.S., Gale T., Lakhani S.R. Molecular evolution of breast cancer. J. Pathol. 2005, 205:248-254.
3. Callagy G., Cattaneo E., Daigo Y., Happerfield L., Bobrow L.G., Pharoah P.D., Caldas C. Molecular classification of breast carcinomas using tissue microarrays. Diagn. Mol. Pathol. 2003, 12:27-34.
4. Cianfrocca M., Gradishar W. New molecular classifications of breast cancer. CA Cancer J. Clin. 2009, 59:303-313.
5. Jonsson G., Staaf J., Vallon-Christersson J., Ringner M., Holm K., Hegardt C., Gunnarsson H., Fagerholm R., Strand C., Agnarsson B.A., Kilpivaara O., Luts L., Heikkila P., Aittomaki K., Blomqvist C., Loman N., Malmstrom P., Olsson H., Johannsson O.T., Arason A., Nevanlinna H., Barkardottir R.B., Borg A. Genomic subtypes of breast cancer identified by array comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res. 2010, 12:R42.
6. Nielsen T.O., Hsu F.D., Jensen K., Cheang M., Karaca G., Hu Z., Hernandez-Boussard T., Livasy C., Cowan D., Dressler L., Akslen L.A., Ragaz J., Gown A.M., Gilks C.B., van de R.M., Perou C.M. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin. Cancer Res. 2004, 10:5367-5374.
7. Perou C.M., Sorlie T., Eisen M.B., van de R.M., Jeffrey S.S., Rees C.A., Pollack J.R., Ross D.T., Johnsen H., Akslen L.A., Fluge O., Pergamenschikov A., Williams C., Zhu S.X., Lonning P.E., Borresen-Dale A.L., Brown P.O., Botstein D. Molecular portraits of human breast tumours. Nature 2000, 406:747-752.
8. Sorlie T., Perou C.M., Tibshirani R., Aas T., Geisler S., Johnsen H., Hastie T., Eisen M.B., van de R.M., Jeffrey S.S., Thorsen T., Quist H., Matese J.C., Brown P.O., Botstein D., Eystein L.P., Borresen-Dale A.L. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. U. S. A 2001, 98:10869-10874.
9. Sorlie T., Tibshirani R., Parker J., Hastie T., Marron J.S., Nobel A., Deng S., Johnsen H., Pesich R., Geisler S., Demeter J., Perou C.M., Lonning P.E., Brown P.O., Borresen-Dale A.L., Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl. Acad. Sci. U. S. A 2003, 100:8418-8423.
10. Pinder S.E., Ellis I.O. The diagnosis and management of pre-invasive breast disease: ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH)-current definitions and classification. Breast Cancer Res. 2003, 5:254-257.
11. Andrianifahanana M., Moniaux N., Schmied B.M., Ringel J., Friess H., Hollingsworth M.A., Buchler M.W., Aubert J.P., Batra S.K. Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin. Cancer Res. 2001, 7:4033-4040.
12. Andrianifahanana M., Moniaux N., Batra S.K. Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases. Biochim. Biophys. Acta 2006, 1765:189-222.
13. Hollingsworth M.A., Swanson B.J. Mucins in cancer: protection and control of the cell surface. Nat. Rev. Cancer 2004, 4:45-60.
14. Senapati S., Das S., Batra S.K. Mucin-interacting proteins: from function to therapeutics. Trends Biochem. Sci. 2010, 35:236-245.
15. Chaturvedi P., Singh A.P., Batra S.K. Structure, evolution, and biology of the MUC4 mucin. FASEB J. 2008, 22:966-981.
16. Hattrup C.L., Gendler S.J. Structure and function of the cell surface (tethered) mucins. Annu. Rev. Physiol. 2008, 70:431-457.
17. Fowler J., Vinall L., Swallow D. Polymorphism of the human muc genes. Front. Biosci. 2001, 6:D1207-D1215.
18. Diaz L.K., Wiley E.L., Morrow M. Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast. Breast J. 2001, 7:40-45.
19. Bafna S., Kaur S., Batra S.K. Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene 2010, 29:2893-2904.
20. Kufe D.W. Mucins in cancer: function, prognosis and therapy. Nat. Rev. Cancer 2009, 9:874-885.
21. Pereira M.B., Dias A.J., Reis C.A., Schmitt F.C. Immunohistochemical study of the expression of MUC5AC and MUC6 in breast carcinomas and adjacent breast tissues. J. Clin. Pathol. 2001, 54:210-213.
22. Workman H.C., Miller J.K., Ingalla E.Q., Kaur R.P., Yamamoto D.I., Beckett L.A., Young L.J., Cardiff R.D., Borowsky A.D., Carraway K.L., Sweeney C., Carraway K.L. The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells. Breast Cancer Res. 2009, 11:R70.
23. de Bolos B.C., Garrido M., Real F.X. MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach. Gastroenterology 1995, 109:723-734.
24. Sonora C., Mazal D., Berois N., Buisine M.P., Ubillos L., Varangot M., Barrios E., Carzoglio J., Aubert J.P., Osinaga E. Immunohistochemical analysis of MUC5B apomucin expression in breast cancer and non-malignant breast tissues. J. Histochem. Cytochem. 2006, 54:289-299.
25. Blair S.L., Wang-Rodriguez J., Cortes-Mateos M.J., Messmer D., Sandoval S., Messmer B., Trogler W., Kummel A. Enhanced touch preps improve the ease of interpretation of intraoperative breast cancer margins. Am. Surg. 2007, 73:973-976.
26. Walsh M.D., McGuckin M.A., Devine P.L., Hohn B.G., Wright R.G. Expression of MUC2 epithelial mucin in breast carcinoma. J. Clin. Pathol. 1993, 46:922-925.
27. Terada T. Ductal adenoma of the breast: immunohistochemistry of two cases. Pathol. Int. 2008, 58:801-805.
28. Demichelis S.O., Alberdi C.G., Servi W.J., Isla-Larrain M.T., Segal-Eiras A., Croce M.V. Comparative immunohistochemical study of MUC1 and carbohydrate antigens in breast benign disease and normal mammary gland. Appl. Immunohistochem. Mol. Morphol. 2010, 18:41-50.
29. Gendler S.J., Spicer A.P., Lalani E.N., Duhig T., Peat N., Burchell J., Pemberton L., Boshell M., Taylor-Papadimitriou J. Structure and biology of a carcinoma-associated mucin, MUC1. Am. Rev. Respir. Dis. 1991, 144:S42-S47.
30. Hanisch F.G., Stadie T.R., Deutzmann F., Peter-Katalinic J. MUC1 glycoforms in breast cancer-cell line T47D as a model for carcinoma-associated alterations of 0-glycosylation. Eur. J. Biochem. 1996, 236:318-327.
31. de Bolos B.C., Guma M., Barranco C., Garrido M., Kim Y.S., Real F.X. MUC6 expression in breast tissues and cultured cells: abnormal expression in tumors and regulation by steroid hormones. Int. J. Cancer 1998, 77:193-199.
32. Borg A., Zhang Q.X., Olsson H., Wenngren E. Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. Genes Chromosom. Cancer 1992, 5:311-320.
33. Cannone M., Oliveri C., Roz E., Rispoli F., Ferrarese S., Alexiadis S., Barberis M.C. Molecular markers of breast cancer cells identified in fine needle aspiration samples from resected sentinel lymph nodes. Acta Cytol. 2006, 50:271-276.
34. Dian D., Janni W., Kuhn C., Mayr D., Karsten U., Mylonas I., Friese K., Jeschke U. Evaluation of a novel anti-mucin 1 (MUC1) antibody (PankoMab) as a potential diagnostic tool in human ductal breast cancer; comparison with two established antibodies. Onkologie 2009, 32:238-244.
35. Ding H.Y., Gao L.X. Spindle cell carcinoma of breast with neuroendocrine differentiation. Zhonghua Bing Li Xue Za Zhi 2006, 35:13-17.
36. Mitas M., Mikhitarian K., Walters C., Baron P.L., Elliott B.M., Brothers T.E., Robison J.G., Metcalf J.S., Palesch Y.Y., Zhang Z., Gillanders W.E., Cole D.J. Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel. Int. J. Cancer 2001, 93:162-171.
37. Rakha E.A., Boyce R.W., Abd El-Rehim D., Kurien T., Green A.R., Paish E.C., Robertson J.F., Ellis I.O. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod. Pathol. 2005, 18:1295-1304.
38. Nguyen M.D., Plasil B., Wen P., Frankel W.L. Mucin profiles in signet-ring cell carcinoma. Arch. Pathol. Lab. Med. 2006, 130:799-804.
39. Lacunza E., Baudis M., Colussi A.G., Segal-Eiras A., Croce M.V., Abba M.C. MUC1 oncogene amplification correlates with protein overexpression in invasive breast carcinoma cells. Cancer Genet. Cytogenet. 2010, 201:102-110.
40. Jones S.E. A new estrogen receptor antagonist-an overview of available data. Breast Cancer Res. Treat. 2002, 75(Suppl 1):S19-S21.
41. Singh A.P., Chaturvedi P., Batra S.K. Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Cancer Res. 2007, 67:433-436.
42. Lacroix-Triki M., Suarez P.H., MacKay A., Lambros M.B., Natrajan R., Savage K., Geyer F.C., Weigelt B., Ashworth A., Reis-Filho J.S. Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type. J. Pathol. 2010, 222:282-298.
43. Matsukita S., Nomoto M., Kitajima S., Tanaka S., Goto M., Irimura T., Kim Y.S., Sato E., Yonezawa S. Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma. Histopathology 2003, 42:26-36.
44. Gunhan-Bilgen I., Zekioglu O., Ustun E.E., Memis A., Erhan Y. Invasive micropapillary carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation. AJR Am. J. Roentgenol. 2002, 179:927-931.
45. Moritani S., Ichihara S., Hasegawa M., Endo T., Oiwa M., Yoshikawa K., Sato Y., Aoyama H., Hayashi T., Kushima R. Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in differential diagnosis?. Hum. Pathol. 2008, 39:666-671.
46. Wang J., Jarrett J., Huang C.C., Satcher R.L., Levenson A.S. Identification of estrogen-responsive genes involved in breast cancer metastases to the bone. Clin. Exp. Metastasis 2007, 24:411-422.
47. Isla L.M., Demichelis S., Crespo M., Lacunza E., Barbera A., Creton A., Terrier F., Segal-Eiras A., Croce M.V. Breast cancer humoral immune response: involvement of Lewis y through the detection of circulating immune complexes and association with Mucin 1 (MUC1). J. Exp. Clin. Cancer Res. 2009, 28:121.
48. Chakraborty S., Bonthu N., Swanson B.J., Batra S.K. Role of mucins in the skin during benign and malignant conditions. Cancer Lett. 2010.
49. Rachagani S., Torres M.P., Moniaux N., Batra S.K. Current status of mucins in the diagnosis and therapy of cancer. Biofactors 2009, 35:509-527.
50. Singh A.P., Senapati S., Ponnusamy M.P., Jain M., Lele S.M., Davis J.S., Remmenga S., Batra S.K. Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer. Lancet Oncol. 2008, 9:1076-1085.
51. Wittel U.A., Goel A., Varshney G.C., Batra S.K. Mucin antibodies-new tools in diagnosis and therapy of cancer. Front. Biosci. 2001, 6:D1296-D1310.
52. Bon G.G., Verheijen R.H., Zuetenhorst J.M., van Kamp G.J., Verstraeten A.A., Kenemans P. Mucin-like carcinoma-associated antigen serum levels in patients with adenocarcinomas originating from ovary, breast and colon. Gynecol. Obstet. Invest 1996, 42:58-62.
53. Ceriani R.L., Peterson J.A., Blank E.W., Lamport D.T. Epitope expression on the breast epithelial mucin. Breast Cancer Res. Treat. 1992, 24:103-113.
54. Pichon M.F., Brun G.L., Hacene K., Basuyau J.P., Riedinger J.M., Eche N., Fulla Y., Charlier-Bret N. Comparison of fifteen immunoassays for the measurement of serum MUC-1/CA 15-3 in breast cancer patients. Clin. Chem. Lab. Med. 2009, 47:985-992.
55. O'Brien D.P., Horgan P.G., Gough D.B., Skehill R., Grimes H., Given H.F. CA15-3: a reliable indicator of metastatic bone disease in breast cancer patients. Ann. R. Coll. Surg. Engl. 1992, 74:9-11.
56. Agrawal A.K., Jelen M., Rudnicki J., Grzebieniak Z., Zysko D., Kielan W., Slonina J., Marek G. The importance of preoperative elevated serum levels of CEA and CA15-3 in patients with breast cancer in predicting its histological type. Folia Histochem. Cytobiol. 2010, 48:26-29.
57. Dixon A.R., Price M.R., Hand C.W., Sibley P.E., Selby C., Blamey R.W. Epithelial mucin core antigen (EMCA) in assessing therapeutic response in advanced breast cancer-a comparison with CA15.3. Br. J. Cancer 1993, 68:947-949.
58. Laessig D., Nagel D., Heinemann V., Untch M., Kahlert S., Bauerfeind I., Stieber P. Importance of CEA and CA 15-3 during disease progression in metastatic breast cancer patients. Anticancer Res. 2007, 27:1963-1968.
59. Kim H.S., Park Y.H., Park M.J., Chang M.H., Jun H.J., Kim K.H., Ahn J.S., Kang W.K., Park K., Im Y.H. Clinical significance of a serum CA15-3 surge and the usefulness of CA15-3 kinetics in monitoring chemotherapy response in patients with metastatic breast cancer. Breast Cancer Res. Treat. 2009, 118:89-97.
60. Geraghty J.G., Coveney E.C., Sherry F., O'Higgins N.J., Duffy M.J. CA 15-3 in patients with locoregional and metastatic breast carcinoma. Cancer 1992, 70:2831-2834.
61. Keshaviah A., Dellapasqua S., Rotmensz N., Lindtner J., Crivellari D., Collins J., Colleoni M., Thurlimann B., Mendiola C., Aebi S., Price K.N., Pagani O., Simoncini E., Castiglione G.M., Gelber R.D., Coates A.S., Goldhirsch A. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann. Oncol. 2007, 18:701-708.
62. Bensouda Y., Andre F., Boulet T., Al-Ghuzlan A., Conforti R., Troalen F., Bourgier C., Errihani H., Spielmann M., Delaloge S. Prevalence of elevated serum CA 15-3 at time of metastatic relapse of breast cancer and correlation with hormone receptor status. Bull. Cancer 2009, 96:923-928.
63. McGuckin M.A., Walsh M.D., Hohn B.G., Ward B.G., Wright R.G. Prognostic significance of MUC1 epithelial mucin expression in breast cancer. Hum. Pathol. 1995, 26:432-439.
64. Bieglmayer C., Szepesi T., Neunteufel W. Follow-up of metastatic breast cancer patients with a mucin-like carcinoma-associated antigen: comparison to CA 15.3 and carcinoembryonic antigen. Cancer Lett. 1988, 42:199-206.
65. Nicolini A., Colombini C., Luciani L., Carpi A., Giuliani L. Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients. Br. J. Cancer 1991, 64:154-158.
66. Cohen A.D., Gopas J., Karplus G., Cohen Y. CA 15-3, mucin-like carcinoma-associated antigen and tissue polypeptide-specific antigen: correlation to disease state and prognosis in breast cancer patients. Isr. J. Med. Sci. 1995, 31:155-159.
67. Kruit A., Tilanus-Linthorst M.M., Boonstra J.G., van Schaik R.H., Grutters J.C., van den Bosch J.M., Ruven H.J. MUC1 568 A/G genotype-dependent cancer antigen 15-3 levels in breast cancer patients. Clin. Biochem. 2009, 42:662-665.
68. Duffy M.J., Evoy D., McDermott E.W. CA 15-3: uses and limitation as a biomarker for breast cancer. Clin. Chim. Acta 2010, 411:1869-1874.
69. Ross J.S., Slodkowska E.A. Circulating and disseminated tumor cells in the management of breast cancer. Am. J. Clin. Pathol. 2009, 132:237-245.
70. Berois N., Varangot M., Sonora C., Zarantonelli L., Pressa C., Lavina R., Rodriguez J.L., Delgado F., Porchet N., Aubert J.P., Osinaga E. Detection of bone marrow-disseminated breast cancer cells using an RT-PCR assay of MUC5B mRNA. Int. J. Cancer 2003, 103:550-555.
71. Zieglschmid V., Hollmann C., Gutierrez B., Krehan A., Kaul S., Bocher O. Heterogeneous expression of tumor-associated genes in disseminated breast cancer cells. Anticancer Res. 2007, 27:1769-1776.
72. Bolke E., Orth K., Gerber P.A., Lammering G., Mota R., Peiper M., Matuschek C., Budach W., Rusnak E., Shaikh S., Dogan B., Prisack H.B., Bojar H. Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients. Eur. J. Med. Res. 2009, 14:359-363.
73. Ren J., Agata N., Chen D., Li Y., Yu W.H., Huang L., Raina D., Chen W., Kharbanda S., Kufe D. Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents. Cancer Cell 2004, 5:163-175.
74. Yin L., Kharbanda S., Kufe D. Mucin 1 oncoprotein blocks hypoxia-inducible factor 1alpha activation in a survival response to hypoxia. J. Biol. Chem. 2007, 282:257-266.
75. Huang L., Chen D., Liu D., Yin L., Kharbanda S., Kufe D. MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin. Cancer Res. 2005, 65:10413-10422.
76. Li Y., Liu D., Chen D., Kharbanda S., Kufe D. Human DF3/MUC1 carcinoma-associated protein functions as an oncogene. Oncogene 2003, 22:6107-6110.
77. Rahn J.J., Shen Q., Mah B.K., Hugh J.C. MUC1 initiates a calcium signal after ligation by intercellular adhesion molecule-1. J. Biol. Chem. 2004, 279:29386-29390.
78. Kam J.L., Regimbald L.H., Hilgers J.H., Hoffman P., Krantz M.J., Longenecker B.M., Hugh J.C. MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and MUC1 binding requires six tandem repeats. Cancer Res. 1998, 58:5577-5581.
79. Regimbald L.H., Pilarski L.M., Longenecker B.M., Reddish M.A., Zimmermann G., Hugh J.C. The breast mucin MUCI as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer. Cancer Res. 1996, 56:4244-4249.
80. Ren J., Raina D., Chen W., Li G., Huang L., Kufe D. MUC1 oncoprotein functions in activation of fibroblast growth factor receptor signaling. Mol. Cancer Res. 2006, 4:873-883.
81. Pochampalli M.R., el Bejjani R.M., Schroeder J.A. MUC1 is a novel regulator of ErbB1 receptor trafficking. Oncogene 2007, 26:1693-1701.
82. Ramasamy S., Duraisamy S., Barbashov S., Kawano T., Kharbanda S., Kufe D. The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol. Cell 2007, 27:992-1004.
83. Bitler B.G., Goverdhan A., Schroeder J.A. MUC1 regulates nuclear localization and function of the epidermal growth factor receptor. J. Cell Sci. 2010, 123:1716-1723.
84. Ligtenberg M.J., Kruijshaar L., Buijs F., van M.M., Litvinov S.V., Hilkens J. Cell-associated episialin is a complex containing two proteins derived from a common precursor. J. Biol. Chem. 1992, 267:6171-6177.
85. Macao B., Johansson D.G., Hansson G.C., Hard T. Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat. Struct. Mol. Biol. 2006, 13:71-76.
86. Ahmad R., Raina D., Trivedi V., Ren J., Rajabi H., Kharbanda S., Kufe D. MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signalling. Nat. Cell Biol. 2007, 9:1419-1427.
87. Leng Y., Cao C., Ren J., Huang L., Chen D., Ito M., Kufe D. Nuclear import of the MUC1-C oncoprotein is mediated by nucleoporin Nup62. J. Biol. Chem. 2007, 282:19321-19330.
88. Wei X., Xu H., Kufe D. MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Mol. Cell 2006, 21:295-305.
89. Pitroda S.P., Khodarev N.N., Beckett M.A., Kufe D.W., Weichselbaum R.R. MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment. Proc. Natl. Acad. Sci. U. S. A 2009, 106:5837-5841.
90. Khodarev N.N., Pitroda S.P., Beckett M.A., MacDermed D.M., Huang L., Kufe D.W., Weichselbaum R.R. MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer. Cancer Res. 2009, 69:2833-2837.
91. Li Y., Yu W.H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D. Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Mol. Cancer Res. 2003, 1:765-775.
92. Khodarev N., Ahmad R., Rajabi H., Pitroda S., Kufe T., McClary C., Joshi M.D., MacDermed D., Weichselbaum R., Kufe D. Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer. Oncogene 2010, 29:920-929.
93. Schroeder J.A., Adriance M.C., Thompson M.C., Camenisch T.D., Gendler S.J. MUC1 alters beta-catenin-dependent tumor formation and promotes cellular invasion. Oncogene 2003, 22:1324-1332.
94. Wei X., Xu H., Kufe D. Human MUC1 oncoprotein regulates p53-responsive gene transcription in the genotoxic stress response. Cancer Cell 2005, 7:167-178.
95. Daniel J.M., Reynolds A.B. The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Mol. Cell. Biol. 1995, 15:4819-4824.
96. Reynolds A.B., Daniel J., McCrea P.D., Wheelock M.J., Wu J., Zhang Z. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol. Cell. Biol. 1994, 14:8333-8342.
97. Fearnhead N.S., Britton M.P., Bodmer W.F. The ABC of APC. Hum. Mol. Genet. 2001, 10:721-733.
98. Sarrio D., Moreno-Bueno G., Hardisson D., Sanchez-Estevez C., Guo M., Herman J.G., Gamallo C., Esteller M., Palacios J. Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int. J. Cancer 2003, 106:208-215.
99. Virmani A.K., Rathi A., Sathyanarayana U.G., Padar A., Huang C.X., Cunnigham H.T., Farinas A.J., Milchgrub S., Euhus D.M., Gilcrease M., Herman J., Minna J.D., Gazdar A.F. Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas. Clin. Cancer Res. 2001, 7:1998-2004.
100. Moll U.M., Riou G., Levine A.J. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc. Natl. Acad. Sci. U. S. A 1992, 89:7262-7266.
101. Carraway K.L., Price-Schiavi S.A., Komatsu M., Jepson S., Perez A., Carraway C.A. Muc4/sialomucin complex in the mammary gland and breast cancer. J. Mammary Gland Biol. Neoplasia 2001, 6:323-337.
102. Komatsu M., Yee L., Carraway K.L. Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells. Cancer Res. 1999, 59:2229-2236.
103. Chaturvedi P., Singh A.P., Chakraborty S., Chauhan S.C., Bafna S., Meza J.L., Singh P.K., Hollingsworth M.A., Mehta P.P., Batra S.K. MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Res. 2008, 68:2065-2070.
104. Funes M., Miller J.K., Lai C., Carraway K.L., Sweeney C. The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. J. Biol. Chem. 2006, 281:19310-19319.
105. Holbro T., Beerli R.R., Maurer F., Koziczak M., Barbas C.F., Hynes N.E. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc. Natl. Acad. Sci. U. S. A 2003, 100:8933-8938.
106. Workman H.C., Sweeney C., Carraway K.L. The membrane mucin Muc4 inhibits apoptosis induced by multiple insults via ErbB2-dependent and ErbB2-independent mechanisms. Cancer Res. 2009, 69:2845-2852.
107. Gilewski T., Adluri S., Ragupathi G., Zhang S., Yao T.J., Panageas K., Moynahan M., Houghton A., Norton L., Livingston P.O. Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin. Cancer Res. 2000, 6:1693-1701.
108. Gulley J.L., Arlen P.M., Tsang K.Y., Yokokawa J., Palena C., Poole D.J., Remondo C., Cereda V., Jones J.L., Pazdur M.P., Higgins J.P., Hodge J.W., Steinberg S.M., Kotz H., Dahut W.L., Schlom J. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin. Cancer Res. 2008, 14:3060-3069.
109. Braun D.P., Crist K.A., Shaheen F., Staren E.D., Andrews S., Parker J. Aromatase inhibitors increase the sensitivity of human tumor cells to monocyte-mediated, antibody-dependent cellular cytotoxicity. Am. J. Surg. 2005, 190:570-571.
110. Yuan S., Shi C., Ling R., Wang T., Wang H., Han W. Immunization with two recombinant Bacillus Calmette-Guerin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice. J. Cancer Res. Clin. Oncol. 2010, 136:1359-1367.
111. Carr-Brendel V., Markovic D., Ferrer K., Smith M., Taylor-Papadimitriou J., Cohen E.P. Immunity to murine breast cancer cells modified to express MUC-1, a human breast cancer antigen, in transgenic mice tolerant to human MUC-1. Cancer Res. 2000, 60:2435-2443.
112. Chen L., Chen D., Manome Y., Dong Y., Fine H.A., Kufe D.W. Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter. J. Clin. Invest. 1995, 96:2775-2782.
113. Akewanlop C., Watanabe M., Singh B., Walker M., Kufe D.W., Hayes D.F. Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody. Cancer Res. 2001, 61:4061-4065.
114. Buckman R., De A.C., Shaw P., Covens A., Osborne R., Kerr I., Reed R., Michaels H., Woo M., Reilly R. Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3. Gynecol. Oncol. 1992, 47:102-109.
115. Engebraaten O., Sivam G., Juell S., Fodstad O. Systemic immunotoxin treatment inhibits formation of human breast cancer metastasis and tumor growth in nude rats. Int. J. Cancer 2000, 88:970-976.
116. Persson J., Backstrom M., Johansson H., Jirstrom K., Hansson G.C., Ohlin M. Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumor cells. Tumour Biol. 2009, 30:221-231.
117. Moniaux N., Varshney G.C., Chauhan S.C., Copin M.C., Jain M., Wittel U.A., Andrianifahanana M., Aubert J.P., Batra S.K. Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans. J. Histochem. Cytochem. 2004, 52:253-261.
118. Dharma R.T., Park K.J., Smith-Jones P., Iasonos A., Linkov I., Soslow R.A., Spriggs D.R. Novel monoclonal antibodies against the proximal (carboxy-terminal) portions of MUC16. Appl. Immunohistochem. Mol. Morphol. 2010, 18:462-472.
119. Block A., Milasinovic D., Mueller J., Schaefer P., Schaefer H., Greten H. Amplified Muc1-specific gene expression in colon cancer cells utilizing a binary system in adenoviral vectors. Anticancer Res. 2002, 22:3285-3292.
120. Nagy P., Friedlander E., Tanner M., Kapanen A.I., Carraway K.L., Isola J., Jovin T.M. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res. 2005, 65:473-482.
121. Price-Schiavi S.A., Jepson S., Li P., Arango M., Rudland P.S., Yee L., Carraway K.L. Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int. J. Cancer 2002, 99:783-791.
122. Fessler S.P., Wotkowicz M.T., Mahanta S.K., Bamdad C. MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells. Breast Cancer Res. Treat. 2009, 118:113-124.
123. Bafna S., Kaur S., Momi N., Batra S.K. Pancreatic cancer cells resistance to gemcitabine: the role of MUC4 mucin. Br. J. Cancer 2009, 101:1155-1161.
124. Domenech N., Henderson R.A., Finn O.J. Identification of an HLA-A11-restricted epitope from the tandem repeat domain of the epithelial tumor antigen mucin. J. Immunol. 1995, 155:4766-4774.
125. Wang H.Y., Fu T., Wang G., Zeng G., Perry-Lalley D.M., Yang J.C., Restifo N.P., Hwu P., Wang R.F. Induction of CD4(+) T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells. J. Clin. Invest. 2002, 109:1463-1470.
126. Viehl C.T., Tanaka Y., Chen T., Frey D.M., Tran A., Fleming T.P., Eberlein T.J., Goedegebuure P.S. Tat mammaglobin fusion protein transduced dendritic cells stimulate mammaglobin-specific CD4 and CD8 T cells. Breast Cancer Res. Treat. 2005, 91:271-278.
127. Yang H., Cho N.H., Seong S.Y. The Tat-conjugated N-terminal region of mucin antigen 1 (MUC1) induces protective immunity against MUC1-expressing tumours. Clin. Exp. Immunol. 2009, 158:174-185.
128. Huyn S.T., Burton J.B., Sato M., Carey M., Gambhir S.S., Wu L. A potent, imaging adenoviral vector driven by the cancer-selective mucin-1 promoter that targets breast cancer metastasis. Clin. Cancer Res. 2009, 15:3126-3134.
129. Raina D., Ahmad R., Joshi M.D., Yin L., Wu Z., Kawano T., Vasir B., Avigan D., Kharbanda S., Kufe D. Direct targeting of the mucin 1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells. Cancer Res. 2009, 69:5133-5141.
130. Cordon-Cardo C. Cancer stem cells. Ann. Oncol. 2010, 21(Suppl 7):vii93-vii94.
131. Engelmann K., Shen H., Finn O.J. MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res. 2008, 68:2419-2426.
132. Miller T.E., Ghoshal K., Ramaswamy B., Roy S., Datta J., Shapiro C.L., Jacob S., Majumder S. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem. 2008, 283:29897-29903.
133. Iorio M.V., Casalini P., Tagliabue E., Menard S., Croce C.M. MicroRNA profiling as a tool to understand prognosis, therapy response and resistance in breast cancer. Eur. J. Cancer 2008, 44:2753-2759.
134. Jin C., Rajabi H., Kufe D. miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death. Int. J. Oncol. 2010, 37:61-69.
135. Sachdeva M., Mo Y.Y. MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res. 2010, 70:378-387.
136. Sachdeva M., Mo Y.Y. miR-145-mediated suppression of cell growth, invasion and metastasis. Am. J. Trans. Res. 2010, 2:170-180.
137. Rajabi H., Jin C., Ahmad R., McClary C., Joshi M.D., Kufe D. MUCIN 1 oncoprotein expression is suppressed by the miR-125b ONCOMIR. Genes Cancer 2010, 1:62-68.