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1.
The effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl lysophospholipid derivative, on the binding of epidermal growth factor (EGF) to human breast cancer cell lines (MCF-7, ZR-75-1, and BT-20), the human epidermoid cancer cell line (A431), and the rat fibroblast cell line (NIH3T3) were investigated. The addition of 10 micrograms/ml ET-18-OCH3 to the growth medium reduced the binding of EGF to hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) and A431 but did not change that to the hormone-independent breast cancer cell line (BT-20). ET-18-OCH3 suppressed the EGF-binding prior to the onset of its inhibitory action on cell growth in MCF-7 and ZR-75-1. Scatchard plot analysis demonstrated that ET-18-OCH3 reduced the number of EGF receptor sites without affecting the affinity of EGF receptors in MCF-7 and ZR-75-1. Both EGF-binding and cell growth in NIH3T3 were not changed by treatment with 10 micrograms/ml ET-18-OCH3. These results suggest that ET-18-OCH3 inhibits the growth of hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) by reducing the binding capacity of EGF receptors and consequently by disturbing the transfer of a variety of growth-promoting signals. 相似文献
2.
Bisphosphonates may induce direct anti-tumor effects in breast cancer cells in vitro. In this study, six bisphosphonates were administered to three breast cancer cell lines. Cell proliferation was measured by quantification of the expression of Cyclin D1 mRNA. Apoptosis was determined by flow cytometry of a DNA fragmentation assay. We demonstrated that bisphosphonates have direct effects on cell proliferation and apoptosis in different breast cancer cell lines. However, not all bisphosphonates act equally on breast cancer cells in vitro. Zoledronate seems to be the most potent of the six bisphosphonates. This in vitro study showed that bisphosphonates possess promising anti-tumor potential. 相似文献
3.
Metastasis from human breast cancer cell lines 总被引:15,自引:0,他引:15
Janet E. Price 《Breast cancer research and treatment》1996,39(1):93-102
Summary Immunodeficient animals, principally nude mice, when used in appropriately designed studies have been shown to be useful for the experimental analysis of human breast cancer metastasis. As with many other human tumors, the implantation of breast cancer cells into an anatomically appropriate tissue (the mammary fatpad) results in increased tumor take and incidence of metastasis for certain cell lines compared with subcutaneous injection. Testing a number of widely available human breast cancer cell lines identified the MDA-MB-435 cell line as the most metastatic, producing lung and lymph node metastases in a high proportion of nude and severe combined immunodeficient (SCID) mice after injection in the mammary fatpad. Mixing human breast cancer cells with normal fibroblasts or with Matrigel also increases the tumor incidence and growth rates in nude mice. Different routes of injection can be used to assess the ability of human breast cancer cells to form metastatic lesions in the lungs (i.v. injection), the liver (injection in the spleen), the brain (direct or intracarotid artery injection) and the bone marrow and bone (injection into the left ventricle of the heart). These different approaches demonstrate the potential of experimental studies of human breast cancer growth and metastasis using immunodeficient mice; this model is valuable for experiments that test the role of metastasis-associated genes and the efficacy of novel forms of therapy. 相似文献
4.
Differential sensitivity of human breast cancer cell lines to the growth-inhibitory effects of tamoxifen 总被引:7,自引:0,他引:7
In eight estrogen receptor (ER)-positive breast cancer cell lines (including three sublines of MCF-7) and five ER-negative breast lines, the action of the nonsteroidal antiestrogen, tamoxifen, was studied, and the concentrations of ER and antiestrogen binding site were measured. The concentration of antiestrogen binding site was significantly [P less than 0.005] greater in ER-positive cells [236,600 +/- 29,900 (SE) sites/cell] than in ER-negative cell lines [66,600 +/- 16,800 sites/cell]. In ER-positive cell lines, a cell cycle phase-specific growth-inhibitory effect, 20% inhibitory dose less than 0.1 to 1.0 microM, was seen which was shown for some representative cell lines to be estrogen reversible. Within this group of cell lines, the degree of tamoxifen-induced inhibition of growth correlated with control population doubling time, but not ER or antiestrogen binding site concentration. The changes in cell cycle kinetic parameters characteristic of all ER-positive lines were a decrease in percentage of S-phase cells and a corresponding increase in percentage of G0-G1 cells. In all cell lines, 5 to 12.5 microM tamoxifen caused cytotoxicity, and this was shown to be estrogen-irreversible in 3 representative cell lines; moreover, estradiol synergistically enhanced the cytotoxic effects of tamoxifen under some experimental conditions. The cell cycle effects of tamoxifen in three ER-negative cell lines (Hs0578T, MDA-MB-231, MDA-MB-330) were decreased proportions of G0-G1 cells with an increase in percentages of S and G2+M cells. These results implied that the mechanism of tamoxifen cytotoxicity may differ in ER-positive and ER-negative breast cancer cells. However, although the ER-negative BT-20 line was much less sensitive to tamoxifen than were the ER-positive cells, growth inhibition and cytotoxicity in this line were associated with a slight decrease in percentage of S-phase cells. These results confirm that ER-positive breast cancer cells are more sensitive (4- to greater than 75-fold) than ER-negative breast cells to the growth-inhibitory effects of tamoxifen and demonstrate that, in all ER-positive cells, growth inhibition and cytotoxicity are accompanied by characteristic changes in cell cycle kinetic parameters. In contrast, different mechanisms may be involved in the effects of tamoxifen on different ER-negative cell lines. 相似文献
5.
Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines. 总被引:8,自引:0,他引:8
The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5-day cultures. Bryostatin 1 inhibited growth of only MCF-7 cells and only at a high dose (100 nM). However, bryostatin 1 completely antagonized the growth inhibition and morphological changes induced by TPA in MCF-7 cells. The divergent effects of these two agents are associated with differing effects on PKC activity and isoform expression in MCF-7 cells. TPA induced rapid translocation of the PKC-alpha isozyme and PKC activity to the membrane fraction of MCF-7 cells. In contrast, bryostatin 1 treatment resulted in the loss of the PKC-alpha isozyme and PKC activity from both cytosolic and membrane compartments within 10 min of treatment. In coincubation assays the bryostatin 1 effect was dominant over that of TPA. Similar effects on PKC-alpha isozyme and PKC activity were seen in a second cell line whose growth was inhibited by TPA but not by bryostatin 1, MDA-MB-468. In contrast, in the T47D cell line, where TPA was not growth inhibitory, TPA failed to induce translocation of PKC-alpha to the cell membrane. Bryostatin, however, still caused loss of PKC-alpha isozyme and PKC activity from cytosolic and membrane fractions. Thus, differential actions of bryostatin 1 and TPA on PKC activity and alpha-isoform level in the membrane-associated fraction of MCF-7 and MDA-MB-468 cells may account for the divergent effects of these two agents on cell growth and morphology. These results suggest that the PKC-alpha isoform may specifically play a role in inhibiting growth of human breast cancer cells. 相似文献
6.
Gloria Calaf Jorge Abarca-Quinones Frank Feuilhade Joelle Beaune Gerard Dupre Mireille Orrico Nandita Barnabas-Sohi J. Claude Kouyoumdjian 《Breast cancer research and treatment》1992,21(1):63-75
Summary Established human mammary tumor cell lines constitute an important tool in the study of breast cancer. The aim of this work was to isolate and characterize two new mammary tumor cell lines, JCK and GCS, which were obtained from the pleural effusion and ascitic fluid, respectively, from two breast cancer patients. Both cell lines had some properties of transformed cells, namely immortalization and growth in soft agar. The carcinoma cells presented epithelial morphology shown by light and electron microscopy, and antigenic properties shown by different tumor markers such as a cytokeratin cocktail, carcinoembryonic antigen, epithelial membrane antigen, and human milk fat globule membrane antigen. A significant increase was also found (P>0.05) in cell growth and3H-thymidine incorporation into DNA in the JCK and GCS cell lines in the presence of 17 estradiol at concentrations of 10–9 and 10–7 M, respectively, after 5 days in culture. These cells presented estradiol receptor levels which were similar in the biopsies and the resulting cell lines. The aromatase activity was also similar in the JCK cell line and the original patient biopsy. However, there was a considerably higher aromatase activity in the GCS cell line than in the biopsy specimen. Southern hybridizations with theneu oncogene showed an additional 12 kb fragment in both cell lines, as also seen in patients with breast cancer. We conclude from these studies that thisin vitro system may provide us with a way to study metastatic cells and improve clinical management of breast cancer patients. 相似文献
7.
The most widely studied steroid hormone responsive cancers are those of the prostate, endometrium and mammary endothelium and the leukaemias. Steroids may in some cases be involved in tumour initiation, and they induce critical events in the malignant 'progression' of these cancers once they develop (after exposure to carcinogens, for example). This paper focuses on the role of the oestrogen receptor as a trigger of cellular growth and invasiveness and as modulator of growth factor secretion in human breast cancer. Growth factor secretion may be a common final pathway of diverse tumorigenic stimuli in a variety of cancers. The finding of external growth control mechanisms suggests possible new ways of therapeutic intervention in breast cancer. 相似文献
8.
Sänger N Strohmeier R Kaufmann M Kuhl H 《European journal of cancer (Oxford, England : 1990)》2000,36(16):2157-2163
The aim of this study was to measure the expression of peripheral benzodiazepine receptors (PBR) as well as mitochondria content in different phases of the cell cycle of BT-20 and MCF-7 breast cancer cell lines, using two-parameter flow cytometric analyses. The PBR expression as well as mitochondria mass, were found to increase as cells pass through different stages of the cell cycle, whereas the amount of PBR in quiescent cells was very low. Binding capacity for the PBR ligand [3H]-Ro5-4864 was strongly related to the phase of the cell cycle with a positive correlation (r=0.98) with a high percentage of cells in S phase. Incubation of BT-20 cells in serum-deprived medium with nanomolar concentrations of Ro5-4864 caused an increase in S phase cells. This effect was not observed in MCF-7 cells. Using micromolar concentrations of Ro5-4864, both BT-20 and MCF-7 cells were reversibly arrested in the G(0/1) phase. 相似文献
9.
目的 比较多药耐药相关蛋白1(MRP1)在人类乳腺癌敏感细胞(MCF-7/S)和耐药细胞(MCF-7/TAM、MCF-7/ADR)中的表达差异。初步探索乳腺癌细胞对三苯氧胺(TAM)和多柔比星(ADR)的耐药性的发生机制。方法 分别采用实时荧光定量PCR、Western blot技术检测MRP1基因和MRP1蛋白在3种乳腺癌细胞中的表达差异。结果 MRP1 mRNA在MCF-7/TAM和MCF-7/ADR细胞中表达量分别是MCF-7/S细胞的(2.63±0.18)倍和(8.38±0.76)倍,差异均有统计学意义(P=0.004,P=0.003)。MRP1蛋白在MCF-7/TAM细胞和MCF-7/ADR细胞中表达均高于MCF-7/S细胞,与MRP1 mRNA的趋势相一致。结论 MRP1的高表达可能是乳腺癌细胞对TAM和ADR产生耐药的共同发生机制。 相似文献
10.
Harkes IC Elstrodt F Dinjens WN Molier M Klijn JG Berns EM Schutte M 《British journal of cancer》2003,89(12):2289-2292
Heterozygous loss of relatively large chromosomal regions is a hallmark of the inactivation of tumour suppressor genes. Searching for deletions in cancer genomes therefore provides an attractive option to identify new tumour suppressor genes. Here, we have performed a genome-wide survey for regions exhibiting allelic loss in 24 commercially available breast cancer cell lines and four breast cancer xenografts, using microsatellite analysis. The assembled allelotype revealed an average fractional allelic loss of 0.34. A total of 19 arms had low allelic loss frequencies (<25%) and 17 arms had moderate allelic loss frequencies (25-50%). Five chromosomal arms were deleted in more than half of the breast cancer samples (8p, 10q, 13q, 17p, and 17q). Three of these frequently lost chromosomal arms had not been identified as such by comparative genome hybridisation, illustrating the higher sensitivity of microsatellite analysis for the detection of allelic losses. As we present allelic loss data of individual samples, our allelotype should not only aid the identification of new breast cancer genes but also provides a baseline for myriad studies involving these breast cancer cell lines. 相似文献
11.
Differentiation state and invasiveness of human breast cancer cell lines 总被引:15,自引:0,他引:15
Connie L. Sommers Stephen W. Byers Erik W. Thompson Jeffrey A. Torri Edward P. Gelmann 《Breast cancer research and treatment》1994,31(2-3):325-335
Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and 1 and 4 integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47DCO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis. 相似文献
12.
Differential characteristics of two newly established human breast carcinoma cell lines 总被引:1,自引:0,他引:1
M Y Chu M G Hagerty M C Wiemann L M Tibbetts S Sato F J Cummings H A Bogaars E H Leduc P Calabresi 《Cancer research》1985,45(3):1357-1366
Two human breast carcinoma cell lines, EP and MW, were established in culture from malignant pleural effusions. In addition to producing tumors in antithymocyte serum-immunosuppressed mice, both cell lines showed epithelial characteristics and anchorage-independent growth in soft agar. EP and MW differed in morphology (spindle-shaped versus round), chromosomal mode (hyperdiploid versus near triploid), estrogen receptor content (43.8 versus 5.1 fmol/mg protein), cloning efficiency (0.24 versus 15%), and activities (milliunits/10(6) cells) of creatine phosphokinase (25.7 versus 62.6) and lactate dehydrogenase (346.7 versus 778.5). Electron microscopy revealed that MW cells had more perinuclear filamentous material and more frequent intracytoplasmic vacuole formation than did EP cells. While having no effect on MW cells at the concentrations studied (10(-5) to 10(-11) M), beta-estradiol (10(-7) M) stimulated the growth of EP cells by 106% over the hormone-depleted control. In a variety of systems, EP was consistently the more drug sensitive of the two lines. In vitro, EP was significantly (p less than 0.001) more sensitive to methotrexate, vincristine, and 5-fluorouracil, respectively. In antithymocyte serum-mouse xenografts, EP displayed a greater response to three different dosages of a combination of cyclophosphamide, methotrexate, and 5-fluorouracil. One such dosage (cyclophosphamide, 32.0 mg/kg/day; methotrexate, 13.0 mg/kg/day; 5-fluorouracil, 190.0 mg/kg/day; for 1 day) reduced EP and MW tumor weights to 5.9 and 41% of controls, respectively. These results correlated well with the clinical responses. 相似文献
13.
Miguel Angel Medina Rocío García de Veas Pilar Morata José Lozano Francisca Sánchez-Jiménez 《Breast cancer research and treatment》1995,35(2):187-194
Summary Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 µM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The antiproliferative effect of CPA was also tested on a poorly-differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231 cells at concentrations higher than 50 µM, and it was also cytotoxic for the colon cancer cell clone 3 at 250 µM CPA. Nevertheless, colon cancer cells were slightly stimulated at CPA concentrations less than 100 µM. CPA reduced (by 50–70%) the ornithine decarboxylase induction occurring early after culture seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents other still unknown cytotoxic effects. 相似文献
14.
Differential regulation of expression of three transforming growth factor beta species in human breast cancer cell lines by estradiol 总被引:10,自引:0,他引:10
Transforming growth factor (TGF)-beta is a potent regulator of many cell functions and a growth inhibitor for mammary epithelial cells. We now know of three highly homologous members of the human TGF-beta gene family. We have studied the expression of TGF-beta 1, -beta 2, and -beta 3 mRNA in four human breast cancer cell lines. Using the RNase protection assay, we have detected mRNA expression of TGF-beta 1, -beta 2, and -beta 3 by T-47D cells, TGF-beta 1 and -beta 3 by ZR-75-1 cells, and TGF-beta 1 by MCF-7 cells. Treatment of these estrogen receptor-positive cells with 10 nM estradiol for 48 h resulted in decreased mRNA levels of TGF-beta 2 and -beta 3 but did not affect mRNA levels of TGF-beta 1. Expression of TGF-beta 1 and -beta 2 mRNA by an estrogen receptor-negative cell line, MDA-MB-231, was not changed by estradiol treatment. Treatment of cells with the antiestrogen tamoxifen (1 microM) did not significantly alter mRNA levels for any of the three TGF-beta species. We have further determined that estradiol treatment of T-47D was associated with diminished secretion of TGF-beta into the medium. Both TGF-beta 1 and -beta 2 inhibited the proliferation of MCF-7 cells, and neither protein affected the growth of T-47D cells. TGF-beta 1 was at least 10-fold more potent than TGF-beta 2 at inhibiting the growth of MCF-7 cells. 相似文献
15.
Walter M. Lewko Rupa Vaghmar Diane Hubbard Marthanna Moore Yun-Ju He Lee Chang Salah Husseini Karen Wallwork Gary B. Thurman Robert K. Oldham 《Breast cancer research and treatment》1990,17(2):121-129
Summary Eighty-five breast cancer specimens were processed as part of a program in tumor acquisition, propagation, and preservation for biotherapy. Nine long-term culture cell lines were developed. Four cell lines were from solid tumor metastases, two lines were from pleural fluid specimens, and three were from xenograft tumors grown in nude mice. Two of the xenograft-derived cell lines were from biopsies which produced tumor cell lines as well. Success in establishing cultures did not correlate with the viability of the biopsy received. Poor tumor cell attachment to culture plastic was the most common problem. For certain specimens, attachment and growth were enhanced on collagen and extracellular matrix substrates. Collagen was beneficial in the development of one cell line. The cell lines were characterized and each of the lines contained more nuclear DNA than found in normal cells. Four of five lines tested were tumorigenic in nude mice. Five of nine were clonogenic in soft agar. Each of the cell lines tested reacted with at least two anti-tumor monoclonal antibodies. Xenograft and biopsy-derived cell lines from the same tumor were similar in their characteristics. While breast cancers are indeed difficult to establish and propagate in culture, the use of xenografts and special substrates appears to be beneficial in the development of cell lines from some tumors. 相似文献
16.
The HMG-I/Y gene encodes the HMG-I and -Y architectural, chromatin binding proteins originally identified based on their association with chromosomal DNA. HMG-I/Y proteins bind to AT-rich regions in chromosomal DNA and alter gene expression. Increased HMG-I/Y protein expression also correlates with neoplastic transformation. Previous work from our laboratory has shown that HMG-I/Y is a direct c-Myc target gene involved in neoplastic transformation in Burkitt's lymphoma. We also observed that HMG-I/Y proteins have several oncogenic properties. In this report, we show that HMG-I/Y proteins are increased in several human breast cancer cell lines compared to a human breast cell line derived from normal breast cells. Decreasing HMG-I/Y proteins using an antisense ribozyme approach inhibits transformation in human breast cancer cells, suggesting that HMG-I/Y is important for the transformed phenotype observed in these cells. In addition, increased expression of the HMG-I isoform in normal human breast cells leads to transformation. These results suggest that HMG-I/Y is an oncogene important in the pathogenesis of human breast cancer. Although additional studies with animal models are needed, the antisense experiments, which result in blocking transformation suggest that this approach may have therapeutic potential in patients with breast cancer characterized by increased HMG-I/Y expression. 相似文献
17.
Bisphosphonates induce apoptosis in human breast cancer cell lines 总被引:23,自引:0,他引:23
Senaratne SG Pirianov G Mansi JL Arnett TR Colston KW 《British journal of cancer》2000,82(8):1459-1468
Breast cancer has a prodigious capacity to metastasize to bone. In women with advanced breast cancer and bone metastases, bisphosphonates reduce the incidence of hypercalcaemia and skeletal morbidity. Recent clinical findings suggest that some bisphosphonates reduce the tumour burden in bone with a consequent increase in survival, raising the possibility that bisphosphonates may have a direct effect on breast cancer cells. We have investigated the in vitro effects of bisphosphonates zoledronate, pamidronate, clodronate and EB 1053 on growth, viability and induction of apoptosis in three human breast cancer cell lines (MDA-MB-231, Hs 578T and MCF-7). Cell growth was monitored by crystal violet dye assay, and cell viability was quantitated by MTS dye reduction. Induction of apoptosis was determined by identification of morphological features of apoptosis using time-lapse videomicroscopy, identifying morphological changes in nucleis using Hoechst staining, quantitation of DNA fragmentation, level of expression of bcl-2 and bax proteins and identification of the proteolytic cleavage of Poly (ADP)-ribose polymerase (PARP). All four bisphosphonates significantly reduced cell viability in all three cell lines. Zoledronate was the most potent bisphosphonate with IC50 values of 15, 20 and 3 microM respectively in MDA-MB-231, MCF-7 and Hs 578T cells. Corresponding values for pamidronate were 40, 35 and 25 microM, whereas clodronate and EB 1053 were more than two orders of magnitude less potent. An increase in the proportion of cells having morphological features characteristic of apoptosis, characteristic apoptotic changes in the nucleus, time-dependent increase in the percentage of fragmented chromosomal DNA, down-regulation in bcl-2 protein and proteolytic cleavage of PARP, all indicate that bisphosphonates have direct anti-tumour effects on human breast cancer cells. 相似文献
18.
E J Sarcione D Delluomo M Zloty 《International journal of cancer. Journal international du cancer》1983,31(2):143-147
Elevated α2PAG serum levels are found in pregnant women and patients with diverse types of neoplasms including breast cancer. Primary human breast cancer tissue, MCF-7 and BT-20 human breast cancer cultured cell lines were shown to synthesize α2PAG in vitro. BT-20 breast cancer cells also released this pregnancy-associated protein. Synthesis was demonstrated by l-[14C]-leucine incorporation into immunochemically isolated protein and confirmed by radioimmunodiffusion and radioimmuno-electrophoresis. These data (1) provide direct evidence for α2PAG synthesis by well-characterized human breast cancer cells per se;(2) strongly suggest that at least part of the α22PAG synthesis observed in primary human breast cancer tissue in vitro was due specifically to breast cancer cells rather than exclusively to monocytes/mac-rophages known to infiltrate neoplastic tissues and to produce this protein during pregnancy; and (3) are consistent with the conclusion that serum α2PAG is a definite breast cancer “marker protein” which originates from and reflects breast cancer status. On the basis of the association of elevated serum α2PAG levels in breast cancer patients, its known immunosuppressive activity in vitro, and the direct evidence for α2PAG synthesis by human breast cancer cells perse, we postulate that this protein plays an important immunoregulatory role in vivo to prevent immune rejection and/or destruction of breast cancer cells. 相似文献
19.
Differential expression of antiapoptotic gene BAG-1 in human breast normal and cancer cell lines and tissues. 总被引:6,自引:0,他引:6
BAG-1 is an antiapoptotic protein that binds to and enhances the antiapoptotic activity of Bcl-2. It binds several growth factor and hormone receptors and modulates their function. BAG-1 was also shown recently to be expressed as four protein isoforms, p50, p46, p33, and p29, through alternative translation initiation. Although many apoptosis-associated genes have been linked to oncogenesis of human breast cancer, the role of BAG-1 has not been fully elucidated. In this study, we examined the expression of BAG-1 RNA or protein isoforms and its interacting antiapoptotic proteins, Bcl-2 and BcI-X(L), in breast normal and tumor cell lines and tissues by Northern or Western blot analysis. We provide convincing evidence that both BAG-1 RNA and protein are overexpressed in human breast cancer cell lines. More importantly, we found that the expression of two isoforms of BAG-1, p46 and p33, was also much higher in breast primary tumors. The expression of Bcl-2 and Bcl-X(L) correlated with that of BAG-1 in breast normal and carcinoma cell lines but not tissues. Our study suggests that BAG-1 isoforms may serve as a molecular marker, independent of Bcl-2 and Bcl-X(L), for human breast cancer. 相似文献
20.
Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin 总被引:22,自引:0,他引:22
Curcumin has anti-inflammatory, antiproliferative, and antitumor effects. To understand the chemopreventive mechanism of curcumin against human malignancies, the cellular and molecular changes induced by this agent in human mammary epithelial (MCF-10A) and breast carcinoma (MCF- 7/TH) cell lines were investigated. The human multidrug- resistant breast cancer cell line was 3.5 fold more sensitive to curcumin than the mammary epithelial cell line. Even though both cell lines accumulated a similar amount of curcumin, a significantly higher percentage of apoptotic cells was induced in breast cancer cells compared to a very low percentage of apoptosis in mammary epithelial cells. Incubation of breast cancer cells with 20 and 40 microM curcumin for 24 h induced G2 block and sub-G0/G1 cell population, respectively. Curcumin treatment caused a reduction in the expression of Ki67, PCNA, and p53 mRNAs in breast cancer cells. The human mammary epithelial cell line showed a down-regulation of p21 mRNA and an up-regulation of Bax mRNA expression with curcumin treatment. The results suggest that apoptosis is involved in the curcumin-induced inhibition of tumor cell growth, and genes associated with cell proliferation and apoptosis may be playing a role in the chemopreventive action of curcumin. 相似文献