On the role of thymopoietins in cell proliferation. Immunochemical evidence for new members of the human thymopoietin family.

Abstract

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 alpha and beta, which are the rat homologs of human TMPOalpha and TMPObeta, respectively. The recent isolation and characterization of seven mouse TMPO mRNA transcripts named TMPO-alpha, beta, beta', gamma, epsilon delta and zeta, suggest that more than the three previously reported transcripts, alpha, beta, and gamma forms, may exist in humans. Here we report on the demonstration of putative human TMPOdelta and epsilon 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-beta-specific, affinity-purified polyclonal antiserum, using a part of the human analog of the beta-specific domain of mouse TMPO 220-259 for immunization. We showed that human TMPObeta 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 TMPObeta in the cancer-derived neuroblastoma cell lines SK-N-MC and SMS-KAN, we found very low expression of human TMPObeta in low-proliferative nerve tissue. These data led us to the assumption that expression of TMPObeta 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.