SMAD4 gene knockdown, using RNA interference strategy or transfection with a dominant negative mutant form of SMAD4, resulted in retained E-cadherin expression in a pancreatic cancer cell line [79]; in association with the abolition of type I collagen synthesis in vitro, and with strong diminished bone metastasis in vivo [80]. The gene discussed is SMAD4; the disease is familial pancreatic carcinoma.