Caveolin-1 expression

M. G. Qaddoumi, H. J. Gukasyan, J. Davda, V. Labhasetwar, K. J. Kim, and V. H. Lee. Clathrin and caveolin-1 expression in primary pigmented rabbit conjunctival epithelial cells role in PLGA nanoparticle endocytosis. Mol Vis 9 559-568 (2003)... 

Carcinogenesis involves a complex series of genetic and biochemical events that enable transformed cells to proliferate, metastasize, migrate to secondary sites, and, sometimes, acquire resistance to chemotherapy. In Sect. 25.4.1, we will discuss how caveolin-1 expression correlates with cancerous growth, a potential mechanism of chemotherapy drug resistance, and how caveolae may be particularly exploited for cancer therapeutic strategies. 

However, as with many stories in science, caveolin expression and oncogenic transformation are a complex and controversial tale. Indeed, numerous other types of cancer cells display increased caveolin-1 expression. For example, caveolin-1 expression has been reported to be overexpressed in several cancers including prostate and breast [52], lung [53], and bladder [54], to name a few. What to make of the dizzying array of caveolin expression data in the context of cancer from a diagnostic or therapeutic standpoint at this time is unclear. 

K. Mellon. Caveolin-1 expression is associated with high-grade bladder cancer. Urology 58 811-814 (2001). 

M. Bagnoli, A. Tomassetti, M. Figini, S. Flati, V. Dolo, S. Canevari, and S. Miotti. Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to alpha-folate receptor overexpression. Oncogene 19 4754-4763 (2000). 

Campbell L, Hollins AJ, Al-Eid A et al (1999) Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures. Biochem Biophys Res Commun 262(3) 744-751 Danto SI, Zabski SM, Crandall ED (1992) Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. Am J Respir Cell Mol Biol 6(3) 296-306... 

Pike LJ, Han X, Chung KN, Gross RW. Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression a quantitative electrospray ionization/mass spectrometric analysis. Biochemistry. 2002 41(6) 2075-2088. 

Kasper M, Reimann T, Hempel U, Wenzel KW, Bierhaus A, Schuh D, Dimmer V, Haroske G, Muller M (1998) Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis. Histochem Cell Biol 109(1) 41—48... 

Koslowski R, Barth K, Augstein A, Tschernig T, Bargsten G, Aufderheide M, Kasper M (2004) A new rat type I-like alveolar epithelial cell line R3/1 bleomycin effects on caveolin expression. Histochem Cell Biol 121 (6) 509—519... 

In MDR cells, a significant fraction of P-gp is found associated with caveolin-rich membranes, and there is a substantial increase in the number of caveolae and caveolin-1 protein level. For example, both multidrug resistant human colon adenocarcinoma HT-29 cells and adriamycin-resistant breast adenocarcinoma MCF-7 cells display about a 12-fold increase in caveolin expression, which correlates with an approximate fivefold increase in morphologically identifiable caveolae [55], In addition, these cells exhibit increased amounts of phospholipase D and lipids such as cholesterol, glucosylceramide, and sphingomyelin [56, 57], Similarly, taxol-resistant A549 cells display both increased caveolin expression and caveolae numbers [58], While these correlations track with MDR, they do not suggest a simple mechanism for the role of... 

Fujita T, Toya Y, Iwatsubo K, et al. Accumulation of molecules involved in ar adrenergic signal within caveolae caveolin expression and the development of cardiac hypertrophy. Cardiovasc Res 2001 51 709-716. 

Ehrhardt C, Kneuer C, Laue M, Schaefer UF, Kim KJ, Lehr CM (2003) 16HBE14o- human bronchial epithelial cell layers express P-glycoprotein, lung resistance-related protein, and caveolin-1. Pharm Res 20(4) 545-551. 

The rat cell line R3/1 was established from cells obtained from broncho-alveolar tissues of foetal Wistar rats at 20 days of gestation. This cell line displays a phenotype with several characteristic features of ATI cells. R3/1 cells were analysed to show a positive expression for mRNA and protein content of markers related to the ATI cell type (e.g., Tla, ICAM-1, connexin-43 and caveolin-1 and -2) [79], Whether or not this cell line can form functional tight junctions is currently under investigation in our laboratories. 

Fuchs S, Hollins AJ, Laue M, Schaefer UF, Roemer K, Gumbleton M, Lehr CM (2003) Differentiation of human alveolar epithelial cells in primary culture— Morphological characterisation and expression of caveolin-1 and surfactant protein-C. Cell Tissue Res 311 31-45... 

J. R. Glenney Jr. and D. Soppet. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc. Natl. Acad. Sci. USA 89 10517— 10521 (1992). 

J. Muller, J. J. Windle, R. G. Pestell, and M. P. Lisanti. 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. 273 20448-20455... 

S. W. Lee, C. L. Reimer, P. Oh, D. B. Campbell, and J. E. Schnitzer. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene 16 1391-1397 (1998). 

It should be noted that the protein caveolin-1 is not necessarily an integral part of caveolae. The so-called lipid-raft mediated pathways have been studied mainly in cells that do not express caveolin-1. Apparently, these mechanisms are similar to caveolae uptake and are therefore discussed in the caveolae section. For detailed reviews on caveolae uptake, see Refs. (25-30). 

Probably the most appropriate marker for this pathway is caveolin-1 tagged with GFP, which after gene expression, is located at sites of caveolae as well as in the Golgi complex (20,26). 

Yera R, Sanchez M, Galisteo M, Villar IC, Jimenez R, Zarzuelo A, Perez-Vizcaino F, Duarte J. 2007. Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats Involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci (Lond) 112 183-191. 

In this chapter, we provide protocols to determine the ability of a peptide to mediate DNA internalization in cultured human tumor cells. Fluorescence-assisted cell sorting (FACS) analysis is used to obtain quantitative data on the time and temperature dependence of macromolecular delivery. Confocal microscopy is used to study the subcellular localization in both fixed and live cells. Fluorescently labeled transferrin and dextran are used to label the clathrin-dependent (15) and the non-clathrin, non-caveolar (16) endocytic compartments, respectively. Expression of a caveolin-l-YFP fusion protein is used to label cell surface caveolae and intracellular caveosomes (17). Finally a protocol, for the overexpression of dominant-negative dynamin [GTPase deficient dynamin-2 containing the amino acid substitution K44A (18)] is provided to evaluate the dynamin dependence of the uptake mechanism. 

Caveoiae represent a subset of lipid rafts found on specific cell types, including adipocytes, endothelia, and muscle cells. These lipid rafts can be observed by electron microscopy as distinctive flask-shaped pits of 60 nm in diameter and include proteins of the caveolin family on the cytoplasmic face of the pit. Lymphocytes and many neuronal cells do not express caveolins and lack these morphological membrane features. Although caveoiae are considered relatively static structures on the cell surface, they can become internalized on binding of... 

These structures can even be induced to form in cells normally lacking caveolae by inducing the expression of caveolin... 

---