Disease relevance of CAV2

• The risk of development of herpes zoster in the CAV1 group was significantly greater than the historical group (p = 0.007) and was also greater than the CAV2 group (p = 0.031) [1].
• In stage I adenocarcinomas, CAV2 protein expression correlated with shorter survival [2].
• Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients [3].
• This enhanced caveolin-2 expression was not detected in active Crohn's disease or ischemic colitis [4].
• Epithelial expression of caveolin-2, but not caveolin-1, is enhanced in the inflamed mucosa of patients with ulcerative colitis [4].

High impact information on CAV2

• Brefeldin A treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD [5].
• The NH(2)- and COOH-terminal domains appeared to be related to membrane binding and exit from ER, respectively, implying that caveolin-2 is synthesized and transported to LD as a membrane protein [5].
• Here, we employ an antisense approach to derive stable NIH 3T3 cell lines that express dramatically reduced levels of caveolin-1 but contain normal amounts of caveolin-2 [6].
• Thus, the phosphorylation of caveolin-2 is a novel mechanism to regulate the dynamics of caveolae assembly [7].
• More importantly, we show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells [7].

Chemical compound and disease context of CAV2

• PURPOSE: To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV) [8].
• Real-time PCR, flow cytometry, and antibody blocking studies suggest that Ad5 and CAV-2 infection ability is not strictly dependent on coxsackie adenovirus receptor (CAR) or alpha(v) integrin levels [9].

Biological context of CAV2

• Alternative termination/polyadenylation generates two CAV2 mRNAs [10].
• The corresponding genes in humans (CAV and CAV2, respectively), have been mapped to a common locus in chromosome 7q31.1, and are possible candidates for the tumor suppressor gene postulated in this region [10].
• The CAV2 promoter region contains two SRE-like boxes resembling those described in the CAV promoter and proposed to link transcription to intracellular cholesterol levels [10].
• Caveolin-1 and caveolin-2 are related proteins involved in the biogenesis of caveolae [10].
• It is likely that the enhanced caveolin-2 expression in patients with UC was associated with the altered signal transductions in the intestinal epithelial cells [4].

Anatomical context of CAV2

• Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells [3].
• When Cav-2 was reintroduced in these cells, it accumulated in the Golgi complex [11].
• The scaffolding domain of caveolin 2 is responsible for its Golgi localization in Caco-2 cells [11].
• In conclusion, we demonstrated that the epithelial expression of caveolin-2 is markedly enhanced in the inflamed mucosa of patients with UC [4].
• In normal colonic mucosa, caveolin-1 expression was detected in the smooth-muscle cells of the muscularis mucosae and the endothelial cells, but caveolin-2 expression was not detected [4].

Associations of CAV2 with chemical compounds

• In the inflamed mucosa of patients with active UC, caveolin-2 expression was clearly detectable as small scattered foci on the luminal surfaces of epithelial cells, but caveolin-1 expression was similar to that in normal mucosa [4].
• Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae and increases the accumulation of noncoated vesicles, but does not affect trafficking of caveolin-2, interaction with caveolin-1 or its biophysical properties [7].
• In addition, analysis of cultured fibroblasts from Cav-1 null embryos reveals the following: (i) a loss of caveolin-2 protein expression; (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein isothiocyanate-albumin; and (iii) a hyperproliferative phenotype [12].
• In human HT-29 colon carcinoma cells, thiazolidinedione PPARgamma ligands increased the levels of caveolin-1 and caveolin-2 proteins two to fivefold in a concentration-dependent manner within 24 h [13].
• D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells [14].

Physical interactions of CAV2

• Cav-2 was able to interact with Cav-1 in the Golgi complex but this interaction was not sufficient to export it from this compartment [11].
• The finding of syndecan-2 reactive with caveolin-2/Ras suggests the molecular complex most likely to obstruct RACK1 for functional attachment at syndecan-2, as revealed in cells transfected with oncogenic ras [15].

Regulatory relationships of CAV2

• Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype [16].
• We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1 [17].

Other interactions of CAV2

• We found that CAV1, CAV2, MET and TES mRNA expression was lower in prostate tumors than in normal prostate tissues [18].
• There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P=0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P=0.029, PgR, P=0.019) [3].
• Caveolin-3 transcript levels increased in 82% of the cohort, along with a 2.5-fold induction of caveolin-2 [19].
• Thus, caveolin-1 expression is required to stabilize the caveolin-2 protein product, to mediate the caveolar endocytosis of specific ligands, to negatively regulate the proliferation of certain cell types, and to provide tonic inhibition of eNOS activity in endothelial cells [12].
• Western analysis demonstrated that mERhigh cells expressed caveolin-1 and caveolin-2, and that ER-alpha was contained in the same gradient-separated membrane fractions [20].

Analytical, diagnostic and therapeutic context of CAV2

• Patients did not receive maintenance chemotherapy (CAV2 protocol) [1].
• Multiple transcriptional start sites spanning 35bp upstream from the CAV2 ATG are detected by 5' RACE, consistent with a TATA-less promoter predicted by sequence analysis [10].
• Semiquantitative RT-PCR analysis showed a 6.5-fold increase in alphaCAV1 mRNA in GC of OF versus DF (P < 0.0001), whereas CAV2 mRNA was increased by only twofold (P < 0.0007) [21].
• In the present study, we showed that caveolin-2, especially its beta isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation [5].
• Ultrastructurally, this pattern of caveolin-2 localization corresponds to caveolae membranes as seen by immunoelectron microscopy [22].

References