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Background  Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the  SMAD4  gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear.    Methods and results  We found a homozygous deletion of the activin A receptor, type IB ( ACVR1B ) gene in 2 out of 8 PC cell lines using array-comparative genomic hybridization, and the absence of  ACVR1B  mRNA and protein expression was confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth and increased the phosphorylation level of SMAD2 and the expression level of p21 CIP1/WAF1  in the Sui66 cell line (wild-type  ACVR1B  and  SMAD4  genes) but not in the Sui68 cell line (homozygous deletion  of ACVR1B  gene). Stable  ACVR1B -knockdown using short hairpin RNA cancelled the effects of activin A on the cellular growth of the PC cell lines. In addition,  ACVR1B -knockdown significantly enhanced the cellular growth and colony formation abilities, compared with controls. In a xenograft study,  ACVR1B -knockdown resulted in a significantly elevated level of tumorigenesis and a larger tumor volume, compared with the control. Furthermore, in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the  ACVR1B  gene, while 10 of the 29 samples (34.5%) carried a deletion of the  SMAD4  gene. Of note, 5 of the 6 samples with a deletion of the  ACVR1B  gene also had a deletion of the  SMAD4  gene.    Conclusion  We identified a homozygous deletion of the  ACVR1B  gene in PC cell lines and clinical samples and proposed that the deletion of the  ACVR1B  gene may mediate an aggressive cancer phenotype in PC. Our findings provide novel insight into the role of the activin signal in PC.

Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer