OBJECTIVE: To investigate the association between the expression of caveolin-1(CAV-1) and the invasion of choriocarcinoma, and to explore the effect of CAV-1 small interfering RNA(siRNA) on the invasion of choriocarcinoma cell line JEG-3. METHODS: (1) Matrigel invasion assay and 3-(4,4)-dimethylthiahiazo (-z-yl)-3,5-di-phenytetrazoliumormide (MTT) assay were used to examine the difference in invasion and proliferation ability between JEG-3 cells and JAR cells;(2) Expression of caveolin-1 gene in the human chorionic villi tissues and chorionicnoma cell lines (JEG-3 cells and JAR cells) were detected by semi-quantitative RT-PCR. (3) The effect of CAV-1 siRNA transfection on the expression of CAV-1 mRNA, and the invasion and proliferation ability of JEG-3 cells were measured by RT-PCR, Matrigel invasion assay and MTT assay. RESULTS: (1) The invasion ability of JEG-3 cell line was stronger than that of JAR cell line (P<0.05), but the difference in proliferation ability between JAR and JEG-3 was not obvious (P>0.05);(2) The expression of caveolin-1 gene in chorionicnoma cell lines was significantly stronger than that in the human normal chorion(P<0.05), and the expression of caveolin-1 gene in JEG-3 cells was stronger than that in the JAR cells (P<0.05). The data suggested that there was significantly positive correlation between caveolin-1 and the invasiveness of chorionicnoma cells (r=0.086,P<0.05);(3) CAV-1 siRNA could knock-out the expression of CAV-1 mRNA, and inhibit the invasion and proliferation ability of chorionicnoma cells. CONCLUSION CAV-1 can promote the invasion ability of chorionicnoma cells. CAV-1 siRNA can inhibit the invasion and proliferation ability of chorionicnoma cells.
Caveolin 1 ; biosynthesis ; genetics ; Choriocarcinoma ; metabolism ; pathology ; Female ; Humans ; Neoplasm Invasiveness ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; Tumor Cells, Cultured ; Uterine Neoplasms ; metabolism ; pathology

This study examined whether genistein influences the production of nitric oxide (NO) and expression of endothelial nitric oxide synthase (eNOS) and the modulators of eNOS activity in ovariectomized (OVX) rat hearts. Female mature Sprague-Dawley rats were subjected to bilateral ovariectomy, OVX rats were randomly divided into four groups: 17beta-estradiol (0.1 mg/kg, s.c. daily) was used as the positive control; low dose of genistein (0.5 mg/kg, s.c. daily); high dose of genistein (5.0 mg/kg, s.c. daily) and model. Sham operations as controls, the treatment lasted 6 weeks. Blood pressure, heart rate, plasma estradiol, heart and uterine weights were measured. Nitrite production in the myocardium was determined by nitrate reductase method. Protein level of eNOS, caveolin-1 and calmodulin was determined by Western blot. The results showed that nitrite production and eNOS protein in homogenized ventricular tissue was attenuated by approximately 53% and 67% in OVX rats compared with those in sham rats, respectively. Genistein increased nitrite production in rat heart in a dose-dependent manner, genistein at the dose of 5 mg/kg.d(-1) resumed nitrite production to a level similar to that in sham operated rats. Administration of genistein also increased eNOS protein expression in OVX rats myocardium with a concomitant decrease in the expression of caveolin-1, an endogenous eNOS inhibitory protein. Another eNOS stimulatory protein, calmodulin, was unchanged in these treatments. These effects were also observed in rats treated with 17beta-estradiol. Genistein at the dose of 5.0 mg/kg.d(-1) augmented uterine weight but this side effect in reproductive system was less than that of 17beta-estradiol. These results suggest that genistein supplementation and estrogen replacement therapy directly increase eNOS functional activity and NO production in the hearts of the OVX rats, but genistein has less side effects on the reproductive system than 17beta-estradiol.
Animals ; Calmodulin ; biosynthesis ; genetics ; Caveolin 1 ; biosynthesis ; genetics ; Dose-Response Relationship, Drug ; Female ; Genistein ; pharmacology ; Myocardium ; metabolism ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type III ; biosynthesis ; genetics ; Ovariectomy ; Phytoestrogens ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

It is well known that exercise can have beneficial effects on insulin resistance by activation of glucose transporter. Following up our previous report that caveolin-1 plays an important role in glucose uptake in L6 skeletal muscle cells, we examined whether exercise alters the expression of caveolin-1, and whether exercise-caused changes are muscle fiber and exercise type specific. Fifity week-old Sprague Dawley (SD) rats were trained to climb a ladder and treadmill for 8 weeks and their soleus muscles (SOL) and extensor digitorum longus muscles (EDL) were removed after the last bout of exercise and compared with those from non-exercised animals. We found that the expression of insulin related proteins and caveolins did not change in SOL muscles after exercise. However, in EDL muscles, the expression of insulin receptor beta (IRbeta) and glucose transporter-4 (GLUT-4) as well as phosphorylation of AKT and AMPK increased with resistance exercise but not with aerobic exercise. Also, caveolin-1 and caveolin-3 increased along with insulin related proteins only in EDL muscles by resistance exercise. These results suggest that upregulation of caveolin-1 in the skeletal muscle is fiber specific and exercise type specific, implicating the requirement of the specific mode of exercise to improve insulin sensitivity.
AMP-Activated Protein Kinases ; Animals ; Caveolin 1/*biosynthesis ; Caveolin 3/metabolism ; Female ; Glucose Transporter Type 4/biosynthesis ; Insulin/*physiology ; Multienzyme Complexes/metabolism ; Muscle Fibers, Skeletal/*metabolism ; Muscle, Skeletal/metabolism/*physiology ; Phosphorylation ; *Physical Conditioning, Animal ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Insulin/biosynthesis ; Up-Regulation

We studied the expression of caveolin-1 in the spinal cords of rats using 60Co gamma-ray irradiation (single dose of 8 Gray (Gy)) in order to determine the possible involvement of caveolin-1 in the tissues of the central nervous system after irradiation. Spinal cords sampled at days 1, 4, and 9 post-irradiation (PI) (n = 5 per each time point) were analyzed by Western blot and immunohistochemistry. Western blot analysis showed that the expression of caveolin-1 was significantly increased at day 1 PI (p < 0.05), and returned to the level of normal control rats on days 4 and 9 PI. Immunohistochemistry showed that caveolin-1 immunoreactivity was enhanced in some glial cells, vascular endothelial cells, and neurons in the spinal cords. The increased expression of glial fibrillary acidic protein (GFAP), a marker for an astroglial reaction, was consistent with that of caveolin-1. In addition, caveolin-1 was co-localized in hypertrophied GFAP-positive astrocytes. Taking all these facts into consideration, we postulate that irradiation induces the increased expression of caveolin-1 in cells of the central nervous system, and that its increased expression in astrocytes may contribute to hypertrophy of astrocytes in the spinal cord after irradiation. The precise role of caveolin-1 in the spinal cords should be studied further.
Animals ; Astrocytes/metabolism/radiation effects ; Blotting, Western ; Caveolin 1/*biosynthesis ; Gamma Rays ; Glial Fibrillary Acidic Protein/*biosynthesis ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/cytology/*metabolism/*radiation effects ; Whole-Body Irradiation

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCCUUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin- 1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell/*diagnosis/*metabolism ; Caveolin 1/*biosynthesis ; Disease Progression ; Disease-Free Survival ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Prognosis ; Urologic Neoplasms/*diagnosis/*metabolism

To study the influence of hypercholesterolemia with caveolin-1 on the plasmalemma of vascular endothelium, we used the methods of immunohistochemistry to detect the dynamic changes of caveolin-1 in cultured ECV-304 cells which were stimulated high cholesterol serum and the arterial endothelium of hypercholesterolemia rats. It is resulted that high cholesteorol level can upregulate the expression of caveolin-1 both in vitro and in vivo. In the initial stage of hypercholesterolemia model, the expression of caveolin-1 increased as the time of high cholesterol level added, but in the later period it was decreased slightly.
Animals ; Aorta ; pathology ; Caveolin 1 ; Caveolins ; biosynthesis ; genetics ; Cells, Cultured ; Cholesterol ; blood ; Endothelium, Vascular ; cytology ; metabolism ; Female ; Humans ; Hypercholesterolemia ; metabolism ; Male ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Umbilical Veins ; cytology

OBJECTIVETo study the expression of caveolin-1 in primary lung cancer and its relationship with microvessel density and clinicopathologic parameters.

METHODSImmunohistochemical study for caveolin-1 and CD34 was performed on paraffin sections of 154 cases of primary lung cancer and adjacent non-neoplastic lung parenchymal tissue, as well as 36 cases with nodal metastasis. Microvessel density was analyzed by CD34 immunostaining. Western blot assay was also employed in tumor and non-neoplastic lung tissues of the 50 cases (25 cases of pulmonary squamous cell carcinoma and 25 cases of pulmonary adenocarcinoma) with fresh specimens available.

RESULTSImmunohistochemical study showed that non-neoplastic bronchial and alveolar epithelium was positive for caveolin-1 (membranous and cytoplasmic). The expression rate of caveolin-1 in lung cancer was 59.1%, which was significantly lower than that in normal lung tissues (P < 0.01). Western blot assay confirmed that the expression of caveolin-1 in pulmonary squamous cell carcinoma and adenocarcinoma was lower than in surrounding non-neoplastic lung tissues (P < 0.01). Caveolin-1 expression in pulmonary small cell carcinoma (7.1%) was significantly lower than that in non-small cell carcinoma (64.3%) (P < 0.01). Within the group of non-small cell carcinoma, the expression of caveolin-1 was much higher in patients with lymph node metastasis (P = 0.005). The expression was also higher in stage III and IV than in stage I and II disease (P = 0.042).

CONCLUSIONSThe expression of caveolin-1 is lower in lung cancer tissues than that in non-small cell carcinoma, it is also significantly correlated with tumor stage and lymph node metastasis. Caveolin-1 may play some role in the progression of pulmonary non-small cell carcinoma.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Caveolin 1 ; biosynthesis ; Female ; Humans ; Immunohistochemistry ; Lung ; chemistry ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Microvessels ; chemistry ; metabolism ; pathology ; Middle Aged ; Neoplasm Staging ; Small Cell Lung Carcinoma ; metabolism ; pathology