On the Role of Thymopoietins in Cell Proliferation. Immunochemical Evidence for New Members of the Human Thymopoietin Family

Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control, as has been shown for lamina-associated polypeptides 2 α and β, which are the rat homologs of human TMPOα and TMPOβ, respectively. The recent isolation and characterization of seven mouse TMPO mRNA transcripts named TMPO-α, β, β', γ, ε, δ, and ζ, suggest that more than the three previously reported transcripts, α, β, and γ forms, may exist in humans. Here we report on the demonstration of putative human TMPOδ and ε by immunoblotting of human cell lines using a newly prepared polyclonal antiserum against the common N-terminal region of TMPO. Furthermore, we prepared the first truly TMPO-β-specific, affinity-purified polyclonal antiserum, using a part of the human analog of the β-specific domain of mouse TMPO 220–259 for immunization. We showed that human TMPOβ is highly expressed in all cancerous cells tested, while hardly any cross-reactivities with other proteins could be detected. In contrast to the high expression of human TMPOβ in the cancer-derived neuroblastoma cell lines SK-N-MC and SMS-KAN, we found very low expression of human TMPOβ in low-proliferative nerve tissue. These data led us to the assumption that expression of TMPOβ may correlate with the occurrence of cancer, and therefore may serve as a new tumor marker, or even as a new target for cancer therapy.