The relationship between telomerase activity and proliferation in cutaneous melanoma Gordana Zamolo a, * , Miran Coklo a , Alan Bosnar a , Tanja Batinac b a Department of Pathology and Forensic Medicine, Rijeka University School of Medicine, B. Branchetta 20, 51000 Rijeka, Croatia b Department of Dermatovenerology, Rijeka University Hospital, Kresimirova 42, 51000 Rijeka, Croatia Received 30 March 2006; accepted 22 April 2006 Summary Telomerase is a ribonucleoprotein reverse transcriptase which RNA component (TERC) and reverse transcriptase (TERT) function together to elongate telomeres. If cells are to survive and proliferate indefinitely, telomere preservation is essential for the immortalization process. Somatic cells rarely possess TA, but over 90% of tumor cells express active telomerase. Increased cell proliferation and deregulation of cell cycle occur in human cancers, including cutaneous melanoma. The exact nature of links between TA, cell proliferation and apoptosis has not been extensively elucidated in cutaneous melanoma. We hypothesize a relationship between TA and cutaneous melanoma cell proliferation in a way that TA in telomere elongation is only an early event in cell immortalization. The telomere elongation makes their proliferation possible and being, at the same time, one of its limiting factors. But the TA other than telomere elongation (TERC independent) is crucial to initiate or restore melanoma cell proliferation. On the other hand, TA in telomere elongation, together with other factors (for example TNF), has an active anti-apoptotic role. This way melanoma cells overwhelm the apoptotic defense mechanisms, finally resulting in their indefinite proliferation. In evaluation of our hypothesis, we suggest thorough studies of both telomerase activity and proliferation in cutaneous melanoma on multiple checkpoints and targets. We also suggest combined analyses of TA and telomere length. This approach seems inevitable since it is obvious that telomerase is no longer just for the elongation of telomeres and, to our knowledge, most of the studies conducted so far evaluated TA as an expression of a single subunit or associated molecule.  c 2006 Elsevier Ltd. All rights reserved. Introduction Telomeres are tandemly repeated TTAGGG se- quences located at the end of human chromosomes [1]. They shorten at each cell division until reach- ing a critical length at which point the cell normally dies [2]. This limits the proliferative potential of normal cells [3]. Telomerase is a ribonucleoprotein reverse trans- criptase that protects chromosomes from degrada- tion by being one of the most important factors in reconstitution of telomeres [1]. Telomerase RNA 0306-9877/$ - see front matter  c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2006.04.073 * Corresponding author. Tel.: +385 51 325 813; fax: +385 51 345 013. E-mail address: gordanazamolo@yahoo.com (G. Zamolo). Medical Hypotheses (2007) 68, 125–127 http://intl.elsevierhealth.com/journals/mehy