AIS is an oncogene amplified in squamous cell carcinoma

AIS is an oncogene amplified in squamous cell carcinoma

^*Department of Otolaryngology–Head and Neck Surgery, Division of Head and Neck Cancer Research, and ^‡Department of Pathology, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196; and ^§Oncogene Research Products, 84 Rogers Street, Cambridge, MA 02142

Communicated by Harry Rubin, University of California, Berkeley, CA (received for review December 22, 1999)

Abstract

We and others recently isolated a human p53 homologue (p40/p51/p63/p73L) and localized the gene to the distal long arm of chromosome 3. Here we sought to examine the role of p40/p73L, two variants lacking the N-terminal transactivation domain, in cancer. Fluorescent in situ hybridization (FISH) analysis revealed frequent amplification of this gene locus in primary squamous cell carcinoma of the lung and head and neck cancer cell lines. (We named this locus AIS for amplified in squamous cell carcinoma.) Furthermore, amplification of the AIS locus was accompanied by RNA and protein overexpression of a variant p68^AIS lacking the terminal transactivation domain. Protein overexpression in primary lung tumors was limited to squamous cell carcinoma and tumors known to harbor a high frequency of p53 mutations. Overexpression of p40^AIS in Rat 1a cells led to an increase in soft agar growth and tumor size in mice. Our results support the idea that AIS plays an oncogenic role in human cancer.

p63 tumor-suppressor gene

Footnotes

↵ † K.H. and B.T. contributed equally to this work.
↵ ¶ To whom reprint requests should be addressed at: Department of Otolaryngology–Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196. E-mail: dsidrans{at}jhmi.edu.
Abbreviations:

TA domain,

transcriptional activation domain;

FISH,

fluorescent in situ hybridization;

HNSCC,

head and neck squamous cell carcinoma;

RT-PCR,

reverse transcription–PCR