Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2007

Open Access 01-12-2007 | Research

Caveolin-1 expression in benign and malignant lesions of the breast

Authors: Cornelia Liedtke, Christian Kersting, Horst Bürger, Ludwig Kiesel, Pia Wülfing

Published in: World Journal of Surgical Oncology | Issue 1/2007

Login to get access

Abstract

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRefPubMed Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRefPubMed
2.
go back to reference Fielding CJ, Fielding PE: Cholesterol and caveolae: structural and functional relationships. Biochim Biophys Acta. 2000, 1529: 210-22.CrossRefPubMed Fielding CJ, Fielding PE: Cholesterol and caveolae: structural and functional relationships. Biochim Biophys Acta. 2000, 1529: 210-22.CrossRefPubMed
3.
go back to reference Li S, Okamoto T, Chun M, Sargiacomo M, Casanova JE, Hansen SH, Nishimoto I, Lisanti MP: Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J Biol Chem. 1995, 270 (26): 15693-15701. 10.1074/jbc.270.26.15693.CrossRefPubMed Li S, Okamoto T, Chun M, Sargiacomo M, Casanova JE, Hansen SH, Nishimoto I, Lisanti MP: Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J Biol Chem. 1995, 270 (26): 15693-15701. 10.1074/jbc.270.26.15693.CrossRefPubMed
4.
go back to reference Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP: Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. J Biol Chem. 1996, 271: 9690-7. 10.1074/jbc.271.16.9690.CrossRefPubMed Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP: Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. J Biol Chem. 1996, 271: 9690-7. 10.1074/jbc.271.16.9690.CrossRefPubMed
5.
go back to reference Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, Lisanti MP, Sessa WC: Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem. 1997, 272: 25437-40. 10.1074/jbc.272.41.25437.CrossRefPubMed Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, Lisanti MP, Sessa WC: Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem. 1997, 272: 25437-40. 10.1074/jbc.272.41.25437.CrossRefPubMed
6.
go back to reference Lisanti MP, Scherer PE, Tang Z, Sargiacomo M: Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol. 1994, 4: 231-5. 10.1016/0962-8924(94)90114-7.CrossRefPubMed Lisanti MP, Scherer PE, Tang Z, Sargiacomo M: Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol. 1994, 4: 231-5. 10.1016/0962-8924(94)90114-7.CrossRefPubMed
7.
go back to reference Koleske AJ, Baltimore D, Lisanti MP: Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci USA. 1995, 92: 1381-5. 10.1073/pnas.92.5.1381.PubMedCentralCrossRefPubMed Koleske AJ, Baltimore D, Lisanti MP: Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci USA. 1995, 92: 1381-5. 10.1073/pnas.92.5.1381.PubMedCentralCrossRefPubMed
8.
go back to reference Suzuoki M, Miyamoto M, Kato K, Hiraoka K, Oshikiri T, Nakakubo Y, Fukunaga A, Shichinohe T, Shinohara T, Itoh T, Kondo S, Katoh H: Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. Br J Cancer. 2002, 87: 1140-4. 10.1038/sj.bjc.6600619.PubMedCentralCrossRefPubMed Suzuoki M, Miyamoto M, Kato K, Hiraoka K, Oshikiri T, Nakakubo Y, Fukunaga A, Shichinohe T, Shinohara T, Itoh T, Kondo S, Katoh H: Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. Br J Cancer. 2002, 87: 1140-4. 10.1038/sj.bjc.6600619.PubMedCentralCrossRefPubMed
9.
go back to reference Yoo SH, Park YS, Kim HR, Sung SW, Kim JH, Shim YS, Lee SD, Choi YL, Kim MK, Chung DH: Expression of caveolin-1 is associated with poor prognosis of patients with squamous cell carcinoma of the lung. Lung Cancer. 2003, 42: 195-202. 10.1016/S0169-5002(03)00287-3.CrossRefPubMed Yoo SH, Park YS, Kim HR, Sung SW, Kim JH, Shim YS, Lee SD, Choi YL, Kim MK, Chung DH: Expression of caveolin-1 is associated with poor prognosis of patients with squamous cell carcinoma of the lung. Lung Cancer. 2003, 42: 195-202. 10.1016/S0169-5002(03)00287-3.CrossRefPubMed
10.
go back to reference Campbell L, Gumbleton M, Griffiths DF: Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma. Br J Cancer. 2003, 89: 1909-13. 10.1038/sj.bjc.6601359.PubMedCentralCrossRefPubMed Campbell L, Gumbleton M, Griffiths DF: Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma. Br J Cancer. 2003, 89: 1909-13. 10.1038/sj.bjc.6601359.PubMedCentralCrossRefPubMed
11.
go back to reference Yang G, Truong LD, Wheeler TM, Thompson TC: Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. Cancer Res. 1999, 59: 5719-23.PubMed Yang G, Truong LD, Wheeler TM, Thompson TC: Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. Cancer Res. 1999, 59: 5719-23.PubMed
12.
go back to reference Engelman JA, Lee RJ, Karnezis A, Bearss DJ, Webster M, Siegel P, Muller WJ, Windle JJ, Pestell RG, Lisanti MP: Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer. J Biol Chem. 1998, 273: 20448-55. 10.1074/jbc.273.32.20448.CrossRefPubMed Engelman JA, Lee RJ, Karnezis A, Bearss DJ, Webster M, Siegel P, Muller WJ, Windle JJ, Pestell RG, Lisanti MP: Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer. J Biol Chem. 1998, 273: 20448-55. 10.1074/jbc.273.32.20448.CrossRefPubMed
13.
go back to reference Zenklusen JC, Bieche I, Lidereau R, Conti CJ: (C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer. Proc Natl Acad Sci USA. 1994, 91: 12155-8. 10.1073/pnas.91.25.12155.PubMedCentralCrossRefPubMed Zenklusen JC, Bieche I, Lidereau R, Conti CJ: (C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer. Proc Natl Acad Sci USA. 1994, 91: 12155-8. 10.1073/pnas.91.25.12155.PubMedCentralCrossRefPubMed
14.
go back to reference Hurlstone AF, Reid G, Reeves JR, Fraser J, Strathdee G, Rahilly M, Parkinson EK, Black DM: Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines. Oncogene. 1999, 18: 1881-90. 10.1038/sj.onc.1202491.CrossRefPubMed Hurlstone AF, Reid G, Reeves JR, Fraser J, Strathdee G, Rahilly M, Parkinson EK, Black DM: Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines. Oncogene. 1999, 18: 1881-90. 10.1038/sj.onc.1202491.CrossRefPubMed
15.
go back to reference Wulfing P, Diallo R, Kersting C, Wulfing C, Poremba C, Rody A, Greb RR, Bocker W, Kiesel L: Expression of endothelin-1, endothelin-A, and endothelin-B receptor in human breast cancer and correlation with long-term follow-up. Clin Cancer Res. 2003, 9: 4125-31.PubMed Wulfing P, Diallo R, Kersting C, Wulfing C, Poremba C, Rody A, Greb RR, Bocker W, Kiesel L: Expression of endothelin-1, endothelin-A, and endothelin-B receptor in human breast cancer and correlation with long-term follow-up. Clin Cancer Res. 2003, 9: 4125-31.PubMed
16.
go back to reference Wulfing P, Diallo R, Muller C, Wulfing C, Poremba C, Heinecke A, Rody A, Greb RR, Bocker W, Kiesel L: Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis. J Cancer Res Clin Oncol. 2003, 129: 375-82. 10.1007/s00432-003-0459-1.CrossRefPubMed Wulfing P, Diallo R, Muller C, Wulfing C, Poremba C, Heinecke A, Rody A, Greb RR, Bocker W, Kiesel L: Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis. J Cancer Res Clin Oncol. 2003, 129: 375-82. 10.1007/s00432-003-0459-1.CrossRefPubMed
17.
go back to reference Holland R, Peterse JL, Millis RR, Eusebi V, Faverly D, van de Vijver MJ, Zafrani B: Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol. 1994, 11: 167-80.PubMed Holland R, Peterse JL, Millis RR, Eusebi V, Faverly D, van de Vijver MJ, Zafrani B: Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol. 1994, 11: 167-80.PubMed
18.
go back to reference Wulfing P, Kersting C, Buerger H, Mattsson B, Mesters R, Gustmann C, Hinrichs B, Tio J, Bocker W, Kiesel L: Expression patterns of angiogenic and lymphangiogenic factors in ductal breast carcinoma in situ. Br J Cancer. 2005, 92: 1720-8. 10.1038/sj.bjc.6602567.PubMedCentralCrossRefPubMed Wulfing P, Kersting C, Buerger H, Mattsson B, Mesters R, Gustmann C, Hinrichs B, Tio J, Bocker W, Kiesel L: Expression patterns of angiogenic and lymphangiogenic factors in ductal breast carcinoma in situ. Br J Cancer. 2005, 92: 1720-8. 10.1038/sj.bjc.6602567.PubMedCentralCrossRefPubMed
19.
go back to reference Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998, 4: 844-7. 10.1038/nm0798-844.CrossRefPubMed Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998, 4: 844-7. 10.1038/nm0798-844.CrossRefPubMed
20.
go back to reference Sagara Y, Mimori K, Yoshinaga K, Tanaka F, Nishida K, Ohno S, Inoue H, Mori M: Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer. Br J Cancer. 2004, 91: 959-65.PubMedCentralPubMed Sagara Y, Mimori K, Yoshinaga K, Tanaka F, Nishida K, Ohno S, Inoue H, Mori M: Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer. Br J Cancer. 2004, 91: 959-65.PubMedCentralPubMed
21.
go back to reference Savage K, Lambros MB, Robertson D, Jones RL, Jones C, Mackay A, James M, Hornick JL, Pereira EM, Milanezi F, Fletcher CD, Schmitt FC, Ashworth A, Reis-Filho JS: Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res. 2007, 13: 90-101. 10.1158/1078-0432.CCR-06-1371.CrossRefPubMed Savage K, Lambros MB, Robertson D, Jones RL, Jones C, Mackay A, James M, Hornick JL, Pereira EM, Milanezi F, Fletcher CD, Schmitt FC, Ashworth A, Reis-Filho JS: Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res. 2007, 13: 90-101. 10.1158/1078-0432.CCR-06-1371.CrossRefPubMed
22.
go back to reference Glenney JR: Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989, 264: 20163-6.PubMed Glenney JR: Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989, 264: 20163-6.PubMed
23.
go back to reference Yang G, Truong LD, Timme TL, Ren C, Wheeler TM, Park SH, Nasu Y, Bangma CH, Kattan MW, Scardino PT, Thompson TC: Elevated expression of caveolin is associated with prostate and breast cancer. Clin Cancer Res. 1998, 4: 1873-80.PubMed Yang G, Truong LD, Timme TL, Ren C, Wheeler TM, Park SH, Nasu Y, Bangma CH, Kattan MW, Scardino PT, Thompson TC: Elevated expression of caveolin is associated with prostate and breast cancer. Clin Cancer Res. 1998, 4: 1873-80.PubMed
24.
go back to reference Pinilla SM, Honrado E, Hardisson D, Benitez J, Palacios J: Caveolin-1 expression is associated with a basal-like phenotype in sporadic and hereditary breast cancer. Breast Cancer Res Treat. 2006, 99: 85-90. 10.1007/s10549-006-9184-1.CrossRefPubMed Pinilla SM, Honrado E, Hardisson D, Benitez J, Palacios J: Caveolin-1 expression is associated with a basal-like phenotype in sporadic and hereditary breast cancer. Breast Cancer Res Treat. 2006, 99: 85-90. 10.1007/s10549-006-9184-1.CrossRefPubMed
25.
go back to reference Kersting C, Packeisen J, Leidinger B, Brandt B, von Wasielewski R, Winkelmann W, van Diest PJ, Gosheger G, Buerger H: Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue sarcomas. J Clin Pathol. 2006, 59: 585-90. 10.1136/jcp.2005.028373.PubMedCentralCrossRefPubMed Kersting C, Packeisen J, Leidinger B, Brandt B, von Wasielewski R, Winkelmann W, van Diest PJ, Gosheger G, Buerger H: Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue sarcomas. J Clin Pathol. 2006, 59: 585-90. 10.1136/jcp.2005.028373.PubMedCentralCrossRefPubMed
26.
go back to reference Williams TM, Medina F, Badano I, Hazan RB, Hutchinson J, Muller WJ: Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J Biol Chem. 2004, 279: 51630-46. 10.1074/jbc.M409214200.CrossRefPubMed Williams TM, Medina F, Badano I, Hazan RB, Hutchinson J, Muller WJ: Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J Biol Chem. 2004, 279: 51630-46. 10.1074/jbc.M409214200.CrossRefPubMed
27.
go back to reference Fiucci G, Ravid D, Reich R, Liscovitch M: Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene. 2003, 21 (15): 2365-2375. 10.1038/sj.onc.1205300.CrossRef Fiucci G, Ravid D, Reich R, Liscovitch M: Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene. 2003, 21 (15): 2365-2375. 10.1038/sj.onc.1205300.CrossRef
28.
go back to reference Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD: Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene. 2006, 25: 7723-39. 10.1038/sj.onc.1209757.CrossRefPubMed Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD: Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene. 2006, 25: 7723-39. 10.1038/sj.onc.1209757.CrossRefPubMed
29.
go back to reference Van den Eynden GG, Van Laere SJ, Van der Auwera I, Merajver SD, Van Marck EA, van Dam P: Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer. Breast Cancer Res Treat. 2006, 95: 219-28. 10.1007/s10549-005-9002-1.CrossRefPubMed Van den Eynden GG, Van Laere SJ, Van der Auwera I, Merajver SD, Van Marck EA, van Dam P: Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer. Breast Cancer Res Treat. 2006, 95: 219-28. 10.1007/s10549-005-9002-1.CrossRefPubMed
30.
go back to reference Shatz M, Liscovitch M: Caveolin-1 and cancer multidrug resistance: coordinate regulation of pro-survival proteins?. Leuk Res. 2004, 28: 907-8. 10.1016/j.leukres.2004.03.013.CrossRefPubMed Shatz M, Liscovitch M: Caveolin-1 and cancer multidrug resistance: coordinate regulation of pro-survival proteins?. Leuk Res. 2004, 28: 907-8. 10.1016/j.leukres.2004.03.013.CrossRefPubMed
31.
go back to reference Marx J: Caveolae: a once-elusive structure gets some respect. Science. 2001, 294: 1862-95. 10.1126/science.294.5548.1862.CrossRefPubMed Marx J: Caveolae: a once-elusive structure gets some respect. Science. 2001, 294: 1862-95. 10.1126/science.294.5548.1862.CrossRefPubMed
32.
go back to reference Pramudji C, Shimura S, Ebara S, Yang G, Wang J, Ren C, Yuan Y, Tahir SA, Timme TL, Thompson TC: In situ prostate cancer gene therapy using a novel adenoviral vector regulated by the caveolin-1 promoter. Clin Cancer Res. 2001, 7: 4272-9.PubMed Pramudji C, Shimura S, Ebara S, Yang G, Wang J, Ren C, Yuan Y, Tahir SA, Timme TL, Thompson TC: In situ prostate cancer gene therapy using a novel adenoviral vector regulated by the caveolin-1 promoter. Clin Cancer Res. 2001, 7: 4272-9.PubMed
33.
go back to reference Boccadoro M, Morgan G, Cavenagh J: Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005, 5: 18-10.1186/1475-2867-5-18.PubMedCentralCrossRefPubMed Boccadoro M, Morgan G, Cavenagh J: Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005, 5: 18-10.1186/1475-2867-5-18.PubMedCentralCrossRefPubMed
Metadata
Title
Caveolin-1 expression in benign and malignant lesions of the breast
Authors
Cornelia Liedtke
Christian Kersting
Horst Bürger
Ludwig Kiesel
Pia Wülfing
Publication date
01-12-2007
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2007
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-5-110

Other articles of this Issue 1/2007

World Journal of Surgical Oncology 1/2007 Go to the issue