AIS is an oncogene amplified in squamous cell carcinoma

We and others recently isolated a human p53 homologue (p40/p51/p63/p73L) an d 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 trans activation domain, in cancer. Fluorescent in situ hybridization (FISH) anal ysis 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, ampl ification of the AIS locus was accompanied by RNA and protein overexpressio n of a variant p68(AIS) lacking the terminal transactivation domain. Protei n overexpression in primary lung tumors was limited to squamous cell carcin oma and tumors known to harbor a high frequency of p53 mutations. Overexpre ssion of p40(AIS) in Rat 1a cells led to an increase in soft agar growth an d tumor size in mice. Our results support the idea that AIS plays an oncoge nic role in human cancer.