Expression of HLA Class-1 Antigens on Renal Cell Carcinoma and
Non-Transformed Renal Tissue

Buszello, H.; Ackermann, R.

doi:10.1159/000474804

Cited by 11 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the panel of 48 renal tumors, 40 had a strong expression of MHC class I antigens, 7 tumors had only weak expression of MHC class I, but none was found to be completely neg ative in all areas of the tumor tissue. This is in accordance to our previous report [9], where 3 of 20 primary RCCs were found to be negative for HLA class I expression. In the literature, there is varying information concerning HLA class I expression in RCC.…”

Section: Human Tissuessupporting

confidence: 93%

“…20 different tumor specimens were examined for the expression of ß2-microglobulin (ß2-m), which is the invariant chain of all HLA class I antigens. However, only 3 RCCs showed reduced HLA class I expression [9], Here we present our results from a study which was done to confirm these results in a larger cohort and with two different monoclonal antibodies (MoAbs), both re cognizing MHC class I molecules. Moreover, we investi gated 12 different métastasés from RCC in order to ana lyze whether the frequency of MHC class I loss in primary tumors is comparable to that in metastatic lesions.…”

Section: Introductionsupporting

confidence: 51%

See 1 more Smart Citation

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Buszello¹,

Ackermann²

1994

Eur Urol

Self Cite

View full text Add to dashboard Cite

Section: Human Tissuessupporting

confidence: 93%

Section: Introductionsupporting

confidence: 51%

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Buszello¹,

Ackermann²

1994

Eur Urol

Self Cite

View full text Add to dashboard Cite

“…This is somewhat similar to clinical studies which reported the importance of 2 m levels in human breast tumors and melanomas (8,9), but not in renal carcinomas (34).…”

Section: Molecular Basis Of 2 M Loss In Mcf-7/adr Cellssupporting

confidence: 89%

Molecular Mechanisms of Loss of β₂-Microglobulin Expression in Drug-Resistant Breast Cancer Sublines and Its Involvement in Drug Resistance

1998

View full text Add to dashboard Cite

In this study, we investigated the mechanism of the loss or decreased expression of beta 2-microglobulin (beta 2m) in several drug-resistant sublines of MCF-7 and in a doxorubicin (DOX)-resistant variant of the T-47D breast cancer cell line. beta 2m protein and RNA are not expressed in highly metastatic, multidrug-resistant MCF-7/Adr cells with high resistance to DOX. Nuclear run-on transcription and RNA stability assays demonstrate that while beta 2m in MCF-7/Adr cells is transcribed, its mRNA is rapidly degraded after synthesis in these cells, indicating that it is controlled by post-transcriptional mechanisms. We also show that an MCF-7 subline (MCF-7/Adr-5) expressing a very low level of resistance to DOX has a decreased level of beta 2m expression. Treatment with actinomycin D revealed that the half-life of beta 2m mRNA in MCF-7 and MCF-7/Adr-5 cell lines was comparable. Nuclear run-on transcription analysis revealed a decreased rate of beta2m transcription in MCF-7/Adr-5 cells compared to that in MCF-7 cells. Moreover, beta 2m mRNA remained undetectable in MCF-7/Adr cells following cycloheximide treatment. However, in MCF-7 cells, increased beta 2m mRNA was observed after 12 h, and a similar level of increased mRNA expression was observed after 36 h of cycloheximide treatment in MCF-7/Adr-5 cells; these results suggest that one of the mechanisms controlling beta 2m mRNA expression might be a negative regulatory protein in MCF-7/Adr-5 cells. Analysis of the beta 2m status of other drug-resistant MCF-7 sublines revealed that deregulation of beta 2m is not limited to DOX resistance, but can also be detected in cells selected for resistance to mAMSA and DOX-verapamil. In addition, our data show that reduced beta 2m expression correlates with the decreased levels of estrogen receptor (ER) expression in the DOX-resistant MCF-7/Adr and T-47D/Adr-4 human breast cell lines. Furthermore, we provide evidence that the partial inhibition of beta 2m by antisense RNA results in 2-3-fold decreased sensitivity of MCF-7 cells to DOX and mAMSA. Moreover, the addition of exogenous beta 2m protein near its physiological human serum concentration can modulate the DOX sensitivity of the MCF-7 antisense beta 2m and control transfectants. Therefore, these results indicate that lost or decreased beta 2m expression is involved in the development of the drug-resistant phenotype and correlates with the loss of ER in human breast cancer cell lines.

show abstract

“…Although the dose-dependent growth and signaling roles of h2M was shown only in a human renal cell carcinoma cell line, these effects are likely to be applicable to human renal cell carcinoma in general because we and others have shown that h2M expression is up-regulated in human renal cancer tissues (24)(25)(26), and that the growth and signaling roles of h2M were observed in other independent studies using human prostate (27), breast, and lung cancer cells. 7 To our knowledge, this is the first report to show the possible directive growth and signaling roles of h2M in human renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 54%

β2-Microglobulin Promotes the Growth of Human Renal Cell Carcinoma through the Activation of the Protein Kinase A, Cyclic AMP–Responsive Element-Binding Protein, and Vascular Endothelial Growth Factor Axis

Nomura

Huang

Zhau

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: h 2 -Microglobulin (h2M), a soluble protein secreted by cancer and host inflammatory cells, has various biological functions, including antigen presentation. Because aberrant expression of h2M has been reported in human renal cell carcinoma, we investigated the effects of h2M overexpression on cancer cell growth and analyzed its molecular signaling pathway. Experimental Design: We established clonal cell lines that overexpressed h2M in human renal cell carcinoma (SN12C) cells and then examined cell growth in vitro and in vivo and studied the h2M-mediated downstream cell signaling pathway. Results: Our results showed that h2M expression positively correlates with (a) in vitro growth on plastic dishes and as Matrigel colonies, (b) cell invasion and migration in Boyden chambers, and (c) vascular endothelial growth factor (VEGF) expression and secretion by cells. We found, in addition, that h2M mediates its action through increased phosphorylation of cyclic AMPr esponsive element-binding protein (CREB) via the protein kinase A-CREB axis, resulting in increased VEGF expression and secretion. In convergence with this signal axis, h2M overexpression also activated both phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. h2M overexpression induced accelerated growth of SN12C in mouse subcutis and bone. Interrupting the h2M signaling pathway using small interfering RNA led to apoptosis with increased activation of caspase-3 and caspase-9 and cleaved poly(ADP-ribose) polymerase. Conclusions: Our results showed for the first time that the h2M-protein kinase A-CREB-VEGF signaling axis plays a crucial role in support of renal cell carcinoma growth and progression and reveals a novel therapeutic target. b 2 -Microglobulin (b2M), a well-known housekeeping gene, is a 12-kDa nonglycosylated polypeptide composed of 100 amino acids. h2M is synthesized by all nucleated cells and forms complexes with the heavy chain of MHC class I (1). MHC class I or HLA antigen plays an important role in tumor immunity because cancer cells present peptides that are degraded by proteasome but still recognized by cytotoxic T cells (2 -4). The expression of MHC class I antigen has been observed in some cancer cells, but down-regulation or loss of HLA molecules on the surface of cancer cells is often associated with the progression of several tumor types (5 -8) due in part to the ability of cancer cells to evade host immune surveillance and subsequent elimination by cytotoxic T cells. However, the biological functions of h2M in cancer and bone metastasis are still unknown.h2M protein expression by normal and cancer cells and its clinical usefulness has been the subject of investigation for the past two decades. With few of these studies showing a direct mitogenic action of h2M (9), no study has attempted to delineate the potential signaling function of h2M in cancer cells. h2M is a soluble factor synthesized and secreted by cancer and inflammatory cells. Increased synthesis and release of h2M occur in seve...

show abstract

Expression of HLA Class-1 Antigens on Renal Cell Carcinoma and Non-Transformed Renal Tissue

Cited by 11 publications

References 10 publications

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Molecular Mechanisms of Loss of β₂-Microglobulin Expression in Drug-Resistant Breast Cancer Sublines and Its Involvement in Drug Resistance

β2-Microglobulin Promotes the Growth of Human Renal Cell Carcinoma through the Activation of the Protein Kinase A, Cyclic AMP–Responsive Element-Binding Protein, and Vascular Endothelial Growth Factor Axis

Contact Info

Product

Resources

About

Expression of HLA Class-1 Antigens on Renal Cell Carcinoma and Non-Transformed Renal Tissue

Cited by 11 publications

References 10 publications

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Immunohistochemical Studies on the Expression of HLA Class I Antigens in Renal Cell Carcinoma: Comparison of Primary and Metastatic Tumor Tissue

Molecular Mechanisms of Loss of β2-Microglobulin Expression in Drug-Resistant Breast Cancer Sublines and Its Involvement in Drug Resistance

β2-Microglobulin Promotes the Growth of Human Renal Cell Carcinoma through the Activation of the Protein Kinase A, Cyclic AMP–Responsive Element-Binding Protein, and Vascular Endothelial Growth Factor Axis

Contact Info

Product

Resources

About

Molecular Mechanisms of Loss of β₂-Microglobulin Expression in Drug-Resistant Breast Cancer Sublines and Its Involvement in Drug Resistance