Recent studies show that activin is implicated in growth arrest of cancer cell proliferation in the early phase of cancer development [4] and [5]. Inhibiting activin binding proteins inhibits human breast cancer cell growth [4] and [5]. Recombinant activin-A reduces breast cancer cell proliferation, arresting the
T7 Tag at G0 [6], and reduces ovarian cancer cell proliferation by 50% [7]. In vivo, activin also inhibits neuroblastoma xenograft tumor growth in mice [8]. Furthermore, mutations in several genes involved in activin signaling pathway were characterized in cancers. Two 8-bp polyadenine tracts of the ActRIIA gene are frequently targeted with frame-shift mutations in gastrointestinal cancers [9] and [10]. Somatic ActRIB (ALK4) gene mutations have also been identified in pancreatic carcinoma [11]. Significant correlations have been observed between a decrease in nuclear Smad3 abundance and high tumor grade, high architectural grade, larger tumor size and hormone
receptor negativity in breast cancer specimens [12], and between Smad3 and cultured breast cancer cell growth inhibition [6]. These data suggest that deregulation of activin or its downstream Smad3 signaling is involved in aberrant cancer cell proliferation.
