||STAT3 transcription factor and Cathepsin L are activated, and play apoptotic roles, during mammary gland involution. The fact that the human CL promoter has a potential STAT binding led to the hypothesis that CL transcription could be regulated by STAT3. STAT3 inhibitor treatment of mice did not result in a decrease in CL mRNA level. In an electrophoretic mobility shift assay, protein present in cells of the mammary gland did contain protein able to bind the CL DNA target sequence, but antibody against STAT3 was not able to supershift the band. Antibodies against other proteins with binding sites within the region used for the gel shift assay, like USF-1, USF-2 and ELK1 also could not supershift the band. These data suggest that an unidentified transcriptional regulatory protein may be responsible for modulating CL expression during involution. Identification of proteins involved in involution can lead to applications in deregulation of proliferation and apoptosis in human tumors.