Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 4, July-August, p. 319–322

Publication type: editorial article

Language: English

The Role of Human PIM−2 (hPIM−2) Gene Expression in Solid Tumors and Hematological Malignancies

Rola ekspresji genu hPIM−2 w nowotworach litych i hematologicznych

Katarzyna Kapelko−Słowik1,, Donata Urbaniak−Kujda1,

1 Chair and Clinic of Hematology, Neoplastic Blood Diseases, and Transplantation, Wroclaw Medical University, Poland

Abstract

Cell survival regulation plays an important role in maintaining homeostasis in response to damaging factors. Neoplastic diseases are those in which failure to maintain an intact apoptotic response is associated with progression and poor response to treatment. Apoptosis is mainly regulated through growth factors and cytokines. One protein which plays a role in apoptosis is serine/threonine kinase PIM−2. PIM−2, PIM−1, and PIM−3 kinases are encoded by the protooncogenes hPIM−1, hPIM−2, and hPIM−3. The mechanism by which PIM−2 kinase promotes cell survival and inhibits apoptosis is still under investigation. The critical moment seems to be inactivation of the pro−apoptotic protein BAD and the translation inhibitor 4E−BP1. The role of hPIM−2 in the oncogenesis of solid tumors and hematological malignances has been well documented. Over−expression of hPIM−2, at both the mRNA and protein level, was observed in human solid tumors and hematological neoplasms. Moreover, it was confirmed that inhibition of hPIM−2 expression blocked cell proliferation and increased cellular apoptosis. Studies on potential anticancer drugs which inhibit PIM−2 kinase are now being conducted.

Streszczenie

Regulacja przeżycia komórek odgrywa wiodącą rolę w utrzymaniu hemostazy w odpowiedzi na czynniki szkodliwe. Niewątpliwie w nowotworach dochodzi do uszkodzenia regulacji procesu apoptozy, co może prowadzić do niekontrolowanego wzrostu i braku odpowiedzi na leczenie przeciwnowotworowe. Apoptoza jest złożonym procesem, w którego regulacji biorą udział cytokiny i czynniki wzrostu. Jednym z białek, które odgrywają rolę w zależnej od czynników wzrostu apoptozie jest kinaza serynowo−treoninowa PIM−2. Kinazy PIM−2 oraz PIM−1 i PIM−3 są kodowane przez odpowiednie protoonkogeny: hPIM−1, hPIM−2, hPIM−3. Mechanizm, w którym PIM−2 hamuje proces apoptozy jest nadal przedmiotem badań. Krytycznym momentem wydaje się inaktywacja proapoptotycznego białka BAD oraz inhibitora translacji 4E−BP1. Rola hPIM−2 w onkogenezie niektórych guzów litych i nowotworów hematologicznych została dobrze udokumentowana. Zwiększoną ekspresję PIM−2, zarówno na poziomie mRNA, jak i białka, stwierdzono w ludzkich nowotworach narządowych i hematologicznych. Wykazano ponadto, że zahamowanie ekspresji hPIM−2 powoduje ograniczenie proliferacji i zwiększenie apoptozy komórek nowotworowych. Obecnie są prowadzone badania na temat inhibitorów kinazy PIM−2 jako potencjalnych leków przeciwnowotworowych.

Key words

hPIM−2, solid tumors, hematological malignances

Słowa kluczowe

hPIM−2, guzy lite, nowotwory hematologiczne

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