Concordant down-regulation of proto-oncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer.
Recognition of tumor cells by cytolytic T lymphocytes depends on cell surface MHC class I expression. As a mechanism to evade T cell recognition, many malignant cancer cells, including those of prostate cancer, down-regulate MHC class I. For the majority of human cancers, the molecular mechanism of MHC class I down regulation is unclear, although it is well established that MHC class I down-regulation is often associated with the down-regulation of multiple genes devoted to antigen presentation. Since the promyelocytic leukemia (PML) proto-oncogene controls multiple antigen-presentation genes in some murine cancer cells, we analyzed the expression of proto-oncogene PML and MHC class I in high-grade prostate cancer. We found that 30 of 37 (81%) prostate adenocarcinoma cases with a Gleason grade of 7-8 had more than 50% down-regulation of HLA class I expression. Among these, 22 cases (73.3%) had no detectable PML protein, while 4 cases (13.3%) showed partial PML down-regulation. In contrast, all 7 cases of prostate cancer with high expression of cell surface HLA class I had high levels of PML expression. Concordant down-regulation of HLA and PML was observed in different histological patterns of prostate adenocarcinoma. These results suggest that in high-grade prostate cancer, malfunction of proto-oncogene PML is a major factor in the down-regulation of cell surface HLA class I molecules, the target molecules essential for the direct recognition of cancer cells by cytolytic T lymphocytes.
Department of Pathology, Division of Cancer Immunology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Huiming
H
Zhang
Jonathan
J
Melamed
Ping
P
Wei
Karen
K
Cox
Wendy
W
Frankel
Robert R
RR
Bahnson
Nikki
N
Robinson
Ron
R
Pyka
Yang
Y
Liu
Pan
P
Zheng
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000071156:Promyelocytic Leukemia Protein; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D025521:Tumor Suppressor Proteins
D015395:Histocompatibility Antigens Class I; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human