Expression and mutation of the tumor suppressor gene p53 in AIDS-associated Kaposi's sarcoma.
Alteration of the p53 gene is the most frequent event reported in human cancer, and p53 mutations have been observed in various neoplasms, including certain forms of skin cancer. Therefore, we postulated that p53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining. Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing data showed the mutation to be located in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also detected in five of the AIDS-KS specimens, two of which also contained p53-positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS.
Li
J J
JJ
Department of Microbiology, New York University Medical Center, New York 10016, USA.
Huang
Y Q
YQ
Cockerell
C J
CJ
Zhang
W G
WG
Nicolaides
A
A
Friedman-Kien
A E
AE
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000032:analysis / Q000235:genetics; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D003062:Codon / Q000235:genetics; D004396:Coloring Agents; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D012514:Sarcoma, Kaposi / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D017501:Adenovirus E1B Proteins; D000952:Antigens, Polyomavirus Transforming; D003062:Codon; D004396:Coloring Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D012194:RNA-Directed DNA Polymerase