THE GENE ENCODING THE P53-REGULATED INHIBITOR OF CDKS (PIC1) IS NOT EXPRESSED IN THE MOLT-4 LEUKEMIA-CELL LINE WITH P53 TRUNCATED AT THE CARBOXYL-TERMINUS, AND HARBORS A NUCLEOTIDE SUBSTITUTION AT CODON-31 IN SEVERAL OTHER CANCER CELL-LINES
Entry into the cell cycle is governed by cyclins, cyclin-dependent kinases (CDKs) and CDK-inhibitors (CDKIs). The p53-regulated inhibitor of CDKs (PIC1) is a universal CDKI whose gene expression is directly induced by the p53 tumor suppressor protein. Reverse transcription and polymerase chain reaction revealed strong PIC1 gene expression in control MRC-5 human embryo lung cells, but relatively weaker bands in A549 lung carcinoma; Hep3B, Mahlavu, PLC/PRF/5 hepatocellular carcinoma; SiHa, CaSki, HeLa cervical carcinoma; T24 bladder carcinoma; MCF7 breast carcinoma; Raji Burkitt lymphoma; HT-1080 fibrosarcoma; and G-401 Wilms' tumor cell lines. These data are consistent with other results obtained by Northern and Western blot and immunoprecipitation techniques, indicating diminished PIC1 expression in cancer cells especially those harboring mutated p53, or human papillomavirus E6 oncoproteins which abrogate p53 activity. PIC1 gene expression was absent in the Molt-4 T-lymphoblastic leukemia cell line with a previously documented alternatively-spliced p53 transcript translating into p53 protein truncated at the carboxyl terminus. It is proposed that this aberrant p53 interferes with the binding of wild-type p53 and other transcription factors to the PIC1 promoter thereby abolishing PIC1 gene expression. This Molt-4 cell line could serve as a useful experimental system for studying the interaction between p53 and other cellular factors with the PIC1 gene. Single-strand conformation polymorphism and direct cycle DNA sequencing analyses demonstrated a PIC1 variant (with an AGC to AGA substitution at codon 31 culminating in a serine to arginine replacement) in Mahlavu, PLC/PRF/5, SiHa, A549 and Raji cell lines. The higher proportion of the PIC1 variant in cancer cell lines (5/13 or 38%) compared with normal individuals (14%), coupled with differences between the predicted secondary structures of the normal and variant PIC1 proteins merit further investigations to elucidate the biological significance of this variant.
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Document Type: Research Article
Publication date: April 1, 1995
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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