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1.
Increased gap junctional intercellular communication capacity and connexin 43 and 26 expression in rat bladder carcinogenesis 总被引:4,自引:0,他引:4
Asamoto Makoto; Takahashi Satoru; Imaida Katsumi; Shirai Tomoyuki; Fukushima Shoji 《Carcinogenesis》1994,15(10):2163-2166
Many reports have suggested that gap junctional intercellularcommunication or gap junction proteins (connexins) could havetumor suppression characteristics. We investigated gap junctionalintercellular communication capacity and connexin 26, 32 and43 mRNA expression in four rat bladder cell lines and the resultswere compared to their tumorigenicity. We also examined connexinexpression in rat bladder carcinomas induced by 3,2'-dlmethyl-4-aminobiphenylor N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and in normalbladders. There was clear tendency that cell lines with greatercommunication had stronger tumorigenicity and more expressionof connexin 26 or 43. We could not detect connexin 32 in thesecell lines. In normal bladder tissue, connexin 43 expressionwas barely detectable and there was no detectable connexin 26.However, in rat bladder carcinomas, especially the EHBNinducedcarcinomas, abundant expression of both connexins was observed.These results indicate that increased gap junctional intercellularcommunication capacity or increased connexin(s) expression maygive a growth advantage in rat bladder carcinogenesis. 相似文献
2.
The dysfunction of homologous and/or heterologous gap junctional intercellular communication (GJIC) has been implicated in tumorigenesis of many kinds of cells. Here we have characterized GJIC and the expression of connexins in six human lung carcinoma cell lines and normal lung fibroblasts (HLF). Compared with HLF, all the carcinoma cells showed reduced or little homologous GJIC. They expressed remarkably reduced connexin(Cx)43 mRNA and variable levels of Cx45 mRNA, but neither Cx43 nor Cx45 protein could be detected. However, using a preloading assay, transfer of calcein was observed between donor HLF cells and first order neighboring recipient tumor cells (recipient cells in 1000-fold excess). Transfer from tumor to HLF cells under the same conditions was not seen, although increasing the ratio of donor tumor cells to recipient HLF cells and plating the cells at low density did reveal weak transfer from tumor cells to HLF. Transfection of Cx43 into giant cell carcinoma PG cells increased homologous communication and eliminated the rectifying behavior of heterologous communication. This indicates that the apparent rectification of dye transfer between normal and tumor cells was a product of low rates of heterologous transfer linked to (i) rapid dilution of the dye to below detectable limits through a very well coupled cell population (tumor to HLF) and (ii) concentration of dye in immediate neighbors in a poorly coupled cell population (HLF to tumor cells). These results suggest that the coupling levels may need to exceed a certain threshold to allow propagation of signals over a sufficient distance to affect behavior of a cell population. We propose that the relative rates of heterologous and homologous coupling of cell populations and the 'pool size' of shared metabolites in tumor cells and the surrounding normal tissue are likely to be very important in the regulation of their growth. 相似文献
3.
Carystinos GD Alaoui-Jamali MA Phipps J Yen L Batist G 《Cancer chemotherapy and pharmacology》2001,47(2):126-132
PURPOSE: Downregulation of gap junctional intercellular communication (GJIC) has been implicated in carcinogenesis. This is a result of altered expression of connexins, the proteins that mediate GJIC, including connexin 43 (Cx43). Our aim was to evaluate the effect of known inducers of Cx43 on the chemosensitivity of the human neuroblastoma cell line IMR-32 to chemotherapeutic agents. METHODS: We examined the effect of dibutyryl-cyclic AMP (db-cAMP) and all-trans-retinoic acid (tRA) on Cx43 and GJIC, glutathione (GSH) and gamma-glutamyl-cysteine-synthetase (gamma-GCS) levels, and glutathione S-transferase (GST) activity. Finally, we performed cell survival assays to measure the response of IMR-32 cells to the chemotherapeutic drugs doxorubicin, melphalan and bis-chloronitrosourea (BCNU), after treatment with db-cAMP and/or tRA. RESULTS: Exposure to db-cAMP led to the upregulation of GJIC and Cx43 expression and phosphorylation. On the other hand, exposure to tRA led to the upregulation of GJIC but Cx43 expression and phosphorylation were not greatly affected. The combination of both agents was more potent in inducing GJIC in comparison to treatment with db-cAMP or tRA alone. Treatment with db-cAMP, but not with tRA, was associated with a significant increase in the cytotoxic effects of the anticancer drugs doxorubicin, melphalan and BCNU as shown by a decrease in their IC50 values. Concomitant exposure to db-cAMP and tRA, however, had a more pronounced effect on cell sensitization to chemotherapy drugs (particularly doxorubicin) than exposure to db-cAMP or tRA alone. Under the db-cAMP and tRA treatment conditions (which upregulate GJIC and modulate drug response), GSH levels were significantly reduced while the levels of GST and gamma-GCS activities remained unchanged. CONCLUSIONS: This study suggests that GJIC plays a role in cellular drug resistance, and highlights the potential use of GJIC modulators in combination with chemotherapy. Also, this is the first study exploring the ability of both db-cAMP and tRA to enhance cell chemosensitivity. 相似文献
4.
Suberoylanilide hydroxamic acid enhances gap junctional intercellular communication via acetylation of histone containing connexin 43 gene locus 总被引:3,自引:0,他引:3
Ogawa T Hayashi T Tokunou M Nakachi K Trosko JE Chang CC Yorioka N 《Cancer research》2005,65(21):9771-9778
A histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induces apoptosis in neoplastic cells, but its effect on gap junctional intercellular communication in relation to apoptosis was unclear. Therefore, we carried out a comparative study of the effects of two HDAC inhibitors, SAHA and trichostatin-A, on gap junctional intercellular communication in nonmalignant human peritoneal mesothelial cells (HPMC) and tumorigenic ras oncogene-transformed rat liver epithelial cells (WB-ras) that showed a significantly lower level of gap junctional intercellular communication than did HPMC. Gap junctional intercellular communication was assessed by recovery rate of fluorescence recovery after photobleaching. Treatment of HPMC with SAHA at nanomolar concentrations caused a dose-dependent increase of recovery rate without inducing apoptosis. This effect was accompanied by enhanced connexin 43 (Cx43) mRNA and protein expression and increased presence of Cx43 protein on cell membrane. Trichostatin-A induced apoptosis in HPMC but was less potent than SAHA in enhancing the recovery rate. In contrast, treatment of WB-ras cells with SAHA or trichostatin-A induced apoptosis at low concentrations, in spite of smaller increases in recovery rate, Cx43 mRNA, and protein than in HPMC. Chromatin immunoprecipitation analysis revealed that SAHA enhanced acetylated histones H3 and H4 in the chromatin fragments associated with Cx43 gene in HPMC. These results indicate that SAHA at low concentrations selectively up-regulates Cx43 expression in normal human cells without induction of apoptosis, as a result of histone acetylation in selective chromatin fragments, in contrast to the apoptotic effect observed in tumorigenic WB-ras cells. These results support a cancer therapeutic and preventive role for specific HDAC inhibitors. 相似文献
5.
Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro. 总被引:11,自引:0,他引:11
E A Hanna S Umhauer S L Roshong M P Piechocki M J Fernstrom J D Fanning R J Ruch 《Carcinogenesis》1999,20(7):1369-1373
Gap junctional intercellular communication (GJIC) and the expression of gap junction proteins (connexins) are frequently decreased in neoplastic cells and have been increased by cAMP and retinoids. GJIC and connexin expression were investigated in early passage normal human ovarian surface epithelial (HOSE) cells, human ovarian adenocarcinoma cell lines (CaOV-3, NIH:OVCAR-3, SK-OV-3 and SW626) and surgical specimens of human serous cystadenocarcinomas. We hypothesized that GJIC and connexin expression would be decreased in neoplastic cells and would be increased by cAMP and retinoic acid. Cultured HOSE cells exhibited extensive fluorescent dye-coupling and connexin43 (Cx43) expression; other connexins were not detected. The ovarian adenocarcinoma cell lines had little dye-coupling or connexin expression. Deletions and rearrangements of the Cx43 gene were not detected by Southern blotting in the carcinoma lines. N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate and all-trans-retinoic acid inhibited cell proliferation, but did not enhance GJIC or Cx43 expression. Surface epithelial cells of benign ovaries expressed Cx43, but this expression was barely detectable in ovarian serous cystadenocarcinomas. Thus, normal HOSE cells had extensive GJIC and Cx43 expression whereas ovarian carcinoma cells had less and cAMP and retinoic acid did not change these, although both agents inhibited cell growth. 相似文献
6.
Kosaku Harada Tetsuo Nonaka Nobuyuki Hamada Hideyuki Sakurai Masatoshi Hasegawa Tomoo Funayama Takehiko Kakizaki Yasuhiko Kobayashi Takashi Nakano 《Cancer science》2009,100(4):684-688
The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5, and 25 cells under confluent cell conditions was irradiated with 1, 5, or 10 particles of carbon ions (220 MeV), and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001–0.002%, 5–25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8–14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas they were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in bystander responses. ( Cancer Sci 2009; 100: 684–688) 相似文献
7.
Upham BL Suzuki J Chen G Wang Y McCabe LR Chang CC Krutovskikh VA Yamasaki H Trosko JE 《Molecular carcinogenesis》2003,37(4):192-201
Gap junctional intercellular communication (GJIC) maintains normal growth and differentiation of cells in a tissue. The intercellular molecules traversing gap junctions are largely unknown, but the molecular weight (MW) cutoff is normally 1200 Da. No differences in dye transfer were observed in normal or vector controls of WB-F344 rat liver epithelial or mouse osteoblastic MC3T3-E1 cells with either Lucifer Yellow (LY) with a MW of 457 Da (LY-457) or LY with a MW of 649 Da (LY-649). Transfection of a dominant negative-connexin 43 (Cx43) gene decreased GJIC (>50%) when LY-649 was used, however, normal GJIC was observed in both cell lines when LY-457 was used. Therefore, the MW cut off in these clones was considerably less than the wild type. The dominant negative clones of the MC3T3-E1 cells exhibited over 90% less alkaline phosphatase (ALPase) activity and calcium deposition after the induction of differentiation. Similarly, dominant negative Cx43 inhibited gene expression of ALPase and bone sialoprotein but not osteocalcin in MC3T3-E1. WB-F344 cells normally exhibit a biphasic response to 12-O-tetradecanoylphorbol-13-acetate (TPA) where inhibition of GJIC recovers after 2 h, but the dominant negative clones showed no recovery from inhibition of GJIC by TPA. Dominant negative Cx43 also inhibited the formation of network-like structures by WB-F344 cells on Matrigel. These results demonstrate that the dominant negative gene transfected into cell types containing the wild-type connexins result in diminished channel sizes, thus allowing the determination of whether distinct biological endpoints, i.e., differentiation, are dependent upon either small or high MW intercellular signals. 相似文献
8.
Gap junction intercellular communication (GJIC) has been measured in cell
lines that represent different stages of chemically induced mouse skin
carcinogenesis. No significant difference in GJIC, as measured by dye
spread, was found in cultures of normal keratinocyte, papilloma or squamous
carcinoma cell lines. There was no correlation, in this system, between the
presence of a mutant Ha-ras gene and down- regulation of communication.
There was, however, a marked decrease in GJIC (80-90%) on progression from
squamous to spindle carcinoma cells. Measurement of GJIC in somatic cell
hybrids shows that the genetic defect responsible for this down-regulation
is recessive and is common to two independently isolated spindle cell
lines. No abnormalities were found in the spindle cells in expression of
connexin 43, a cell component involved in gap junction formation and
permeability. However, expression of E-cadherin, a cell-cell adhesion
molecule implicated in the process of gap junction formation, was missing
in the spindle carcinoma cells. Introduction of an E-cadherin cDNA into the
spindle cells partially restored junctional communication without causing
any noticeable alterations in cell morphology. During the study a non-
tumourigenic keratinocyte line, a sub-clone of a normal keratinocyte line,
was also found to have a low level of GJIC. However, the defect in this
line was shown, by genetic complementation in somatic cell hybrids, to be
different from that in the spindle carcinoma cell lines. Consistent with
these data, analysis by immunofluorescence shows an abnormal distribution
of connexin 43 in these cells.
相似文献
9.
Consumption of dietary carotenoids has been statistically associated with decreased risk of cancer at several anatomic sites. In a model murine system of carcinogenesis (the 10T1/2 assay), we have previously shown that carotenoids can inhibit chemically and physically induced neoplastic transformation. This action is strongly correlated with the ability of carotenoids to increase gap-junctional communication (GJC) by induction of connexin43 (Cx43) gene expression. Here we extend these studies to human foreskin-derived dermal fibroblasts and keratinocytes. In fibroblasts, β-carotene and canthaxanthin at concentrations between 10?5 and 3 × 10?6 M were found to strongly enhance GJC in a dose- and time-dependent manner. This was accompanied by an increase in the number of immunofluorescent junctional plaques recognized by an anti-Cx43 antibody and by an increase in Cx43 protein level as determined by western blot analysis. No decrease in proliferation rates was detected by [H3]thymidine labeling. Human keratinocytes grown in monolayer culture did not respond to carotenoids in terms of GJC as measured by dye transfer, immunofluorescent analysis of Cx43 distribution, or Cx43 levels as measured by western blotting. Both cell types accumulated high levels of carotenoids. Because canthaxanthin, which has no known provitamin A activity in mammals, is as active in fibroblasts as is β-carotene, the carotenoid with the highest provitamin A activity, the induction of GJC and Cx43 expression by carotenoids in human dermal fibroblasts seems unrelated to their provitamin A status. The lack of response of keratinocytes suggests differences in regulation of Cx43 expression or in carotenoid processing. © 1995 Wiley-Liss Inc. 相似文献
10.
Jacqueline M. Park Jessian L. Munoz Brian Wong Won Sarah A. Bliss Steven J. Greco Shyam A. Patel Mustapha Kandouz Pranela Rameshwar 《Cancer letters》2013
Despite ongoing attempts to improve the overall breast cancer (BC) survival rate, BC cells’ (BCCs) predilection for metastasizing to the bone marrow has enabled BCCs to not only remain dormant, but also evade detection. BCCs are able to acquire quiescence by establishing gap junctional intercellular communication (GJIC) with the stroma through the assembly of connexins (Cxs). The chemoattractant CXCL12 also appears to play a role in GJIC based on its tendency to decrease when GJIC is formed between BCCs and bone marrow stroma. This study investigates the role CXCL12 has on Cx43 expression and PKC-mediated Cx43 phosphorylation. Cx43 gene reporter assays revealed that as the BCCs come in contact with each other and establish GJIC, there is an inverse relationship between CXCL12 level and Cx43 expression. Immunoblot analyses confirmed this relationship at the level of protein, showing decreased Cx43 and reduced Cx43 phosphorylation at higher CXCL12 concentrations. However, real-time PCR studies revealed little change in Cx43 mRNA levels, despite stimulation with different concentrations of CXCL12, indicating CXCL12’s effect on Cx43 is post-translational, through phosphorylation. Immunoblot analyses and functional dye exchange studies showed activation of PKC by exogenous CXCL12 in the phosphorylation, which in turn, increased intercellular communication. These findings elucidate the importance of considering the microenvironment’s role in micrometastasis in clinical studies pertaining to prospective breast cancer treatment. 相似文献
11.
In this study, we investigated whether the tumor promoters, 12-O-
tetradecanoylphorbol-13-acetate (TPA), phenobarbital (PB), and 1,1-
bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), inhibited gap junctional
intercellular communication (GJIC) in a cell-specific or connexin-specific
manner and whether protein kinase C was involved. To do this, we used
highly communicating WB-F344 rat liver epithelial cells, which express
connexin43 as their predominant gap junction protein, WB-aB1 cells, which
are a GJIC-incompetent mutant line of WB- F344 cells and that express
connexin43, WB-a/32-10 cells, which are a highly communicating derivative
of WB-aB1 cells generated by stable transduction with a connexin32
retroviral expression vector, and primary cultured rat hepatocytes, which
express conexin32 predominantly. Treatment of WB-F344 and WB-a/32-10 cells,
but not hepatocytes, with TPA inhibited GJIC (assayed by Lucifer Yellow dye
microinjection). This inhibition involved protein kinase C because (i)
inhibition was prevented by co-treatment of the cells with a specific
protein kinase C inhibitor, bis-indolylmaleimide, and (ii) treatment with
TPA for 24 h had no effect on dye-coupling in agreement with the
downregulation of protein kinase C. TPA also caused the internalization of
Cx43-containing gap junctions and the formation of a hyperphosphorylated
form of Cx43, Cx43-P3, in WB-F344 cells only, but TPA had no effect on
Cx32-containing gap junctions or protein mobility. In contrast, PB
inhibited GJIC only in hepatocytes and DDT inhibited GJIC in all three
types of cells; bis-indolylmaleimide did not block the effects of either
agent. These results indicate that the inhibitory actions of TPA and PB on
GJIC are cell-specific rather than connexin- specific and that TPA inhibits
connexin43 and connexin32-mediated GJIC through a protein kinase
C-dependent mechanism.
相似文献
12.
Modulation of gap junctional intercellular communication by EGF in human kidney epithelial cells 总被引:3,自引:1,他引:2
Modulation of gap junctional intercellular communication (GJIC)was studied in a multistep model of human renal epithelial carcinogenesis.We report that the majority of primary human kidney epithelialcells (NHKE) grown from fetal kidney explants did not communicatethrough gap junctions. Communication could, however, be observedwithin a subpopulation of the cells. Ni(II)-immortalized cells(IHKE) showed GJIC at a level of 1020 communicating cells,but with heterogeneous regions on the dish, with regard to bothcommunication and distribution of connexin43. The heterogeneitywas less pronounced in a ras-transfected tumourigenic cell line(THKE), which also showed communication of 相似文献
13.
14.
Overexpression of estrogen receptor-alpha gene suppresses gap junctional intercellular communication in endometrial carcinoma cells 总被引:1,自引:0,他引:1
Stimulation of the endometrium by estrogens without the differentiating effect of progestins is the primary etiological factor associated with the development of endometrial hyperplasia and adenocarcinoma. However, the correlation between sex steroids and gap junctional intercellular communication (GJIC), which is considered to play an important role in the control of cell growth and differentiation, is not well known in endometrial carcinoma. In this study, we focused on the influence of estrogen and its receptor in connexin (Cx) expression and GJIC in endometrial carcinoma cells, established stable clone IK-ER1 overexpressing ER-alpha to transfect the expression vector and analysed them in various hormonal conditions. The growth of IK-ER1 was accelerated by 17beta-estradiol and the acceleration of the 5-bromo-25-deoxyuridine labeling index was observed. GJIC was assayed by scoring the number of dye-coupled cells after microinjection of single cells with Lucifer-Yellow, and subcellular localization of Cx26 and Cx32 was analysed by immunocytochemistry. In the presence of estradiol, dye-coupled cells of IK-ER1 were significantly reduced compared to those without estradiol and the reduction was completely inhibited by adding ICI182.780, a pure antiestrogen substrate. Cxs were detected as only small spots by immunocytochemistry, and Western blotting showed that the expression was decreased. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and suppressing GJIC via suppression of the expression of Cxs in endometrial carcinogenesis. 相似文献
15.
Many studies have correlated reductions in gap junctional intercellular communication (a) with altered cellular growth, tumor promotion, and neoplastic transformation. To test directly whether reduced GJIC affects cellular growth, GJIC was inhibited in murine BALB/c 3T3 fibroblasts by treatment with a phosphorothioatemodified antisense oligonucleotide targeted against the connexin43 translation start codon, and in vitro cell growth was monitored. The cells were incubated with the oligonucleotide (0.1-0.5 μM) in liposomes in serumless culture medium for 16 h; washed and refed with serum-containing medium; and analyzed for dye-coupling, connexin43 protein and mRNA levels, and cell growth over the next 5 d. The antisense oligonucleotide inhibited dye-coupling and reduced connexin43 protein levels in a concentration-dependent manner but had no effect on connexin43 mRNA levels. Cell growth rate was not affected, but saturation density was increased approximately threefold by the oligonucleotide. These data support a role for GJIC in the establishment of contact inhibition of in vitro cell growth. © 1995 Wiley- Liss, Inc. 相似文献
16.
17.
Carotenoids are plant pigments whose consumption is associated with lower cancer rates in humans. Studies in experimental animal and cell systems have confirmed the cancer chemopreventive activity of these compounds. However, their extremely hydrophobic nature makes these compounds biologically unavailable unless delivered in organic solution to model systems. We have synthesized novel disodium salt disuccinate astaxanthin derivatives that possess high aqueous dispersibility. When delivered to mouse embryonic fibroblast C3H/10T1/2 cell cultures, either in aqueous or aqueous/ethanol solutions, these derivatives are biologically active. Biological activity was demonstrated by (1) upregulated expression of connexin 43 (Cx43) protein; (2) increased formation of Cx43 immunoreactive plaques in regions of the plasma membrane consistent with localization of gap junctions; (3) significantly upregulated gap junctional intercellular communication (GJIC) as demonstrated by Lucifer Yellow dye transfer after microinjection (P < 0.03; Fisher's Exact test). Enhanced expression of Cx43 and increased GJIC have been previously demonstrated to result in inhibition of in vitro neoplastic transformation of 10T1/2 cells as well as growth reduction of human tumors in xenografts. These novel derivatives possess increased utility as water soluble and water dispersible agents, allowing for aqueous delivery both in vitro and in vivo, properties that could enhance their potential clinical utility as potent cancer chemopreventive agents. 相似文献
18.
Altered gap junctional intercellular communication in neoplastic rat esophageal epithelial cells 总被引:2,自引:1,他引:2
Gap junctional intercellular communication (GJIC) is reduced in many
neoplastic cells, but few data exist for esophageal neoplasms. GJIC was
examined by fluorescent dye microinjection in two nontumorigenic and two
highly tumorigenic rat esophageal epithelial cell lines. All lines
expressed high levels of dye coupling in homologous cell culture. In
cocultures of nontumorigenic and tumorigenic cells, however, only one of
six cell combinations displayed significant heterologous GJIC. Northern,
Western, and immunohistochemical analyses indicated that all four cell
lines expressed comparable levels of connexin43 (Cx43), but not connexin32
or connexin26, and formed Cx43-containing gap junction plaques at cell-cell
interfaces. Immunostaining of rat esophageal frozen sections demonstrated
that esophageal epithelial cells expressed Cx43 in vivo. In normal
epithelium, the highest expression was seen in the basal cells and little
suprabasal staining was evident. In preneoplastic and neoplastic lesions of
the esophageal epithelium which were induced by treating rats with
N-nitrosomethylbenzylamine, Cx43 staining of the basal layer was also seen
but appeared to be more diffuse compared to normal epithelium. In addition,
suprabasal Cx43 staining was apparent in dysplastic and papillomatous
lesions. These results indicate that Cx43 is expressed in normal and
neoplastic rat esophageal cells and that the cells exhibit extensive
homologous GJIC, but little heterologous GJIC. This lack of heterologous
GJIC may be due to differences in cell adhesion proteins or other factors.
相似文献
19.
20.
E Tomai H L Brownell T V Tufescu K Reid B G Campling L Raptis 《Lung cancer (Amsterdam, Netherlands)》1999,23(3):223-231
Animal tumor models have demonstrated a close correlation between gap junctional, intercellular communication (GJIC) and tumor metastasis. To examine GJIC levels in human lung carcinoma cells, a novel technique was developed: cells were grown on a glass slide, half of which was coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse which opens transient pores on the plasma membrane was applied in the presence of the fluorescent dye, Lucifer yellow, causing the dye's penetration into the cells growing on the conductive part of the slide. The migration of the dye through gap junctions to the non-electroporated cells growing on the non-conductive area was then observed microscopically under fluorescence illumination. The results show that this is a rapid, precise and highly reproducible assay for GJIC assessment in lines established from lung carcinomas or freshly explanted lung tumor cells. Out of 17 established lines only two had extensive junctional communication, while out of 16 fresh tumor specimens none displayed GJIC. On the other hand, fibroblasts isolated from the same tumors had extensive junctional permeability. The examination of GJIC in a large number of samples could establish a correlation between GJIC and metastasis which might have prognostic value. 相似文献