γ-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells

Katsunori Fujii, Toshiyuki Miyashita, Jun Ichi Takanashi, Katsuo Sugita, Yoichi Kohno, Haruko Nishie, Shin Ichiro Yasumoto, Masutaka Furue, Masao Yamada

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Abstract

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that γ-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after γ-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after γ-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after γ-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.

Original languageEnglish
Pages (from-to)1351-1357
Number of pages7
JournalJapanese Journal of Cancer Research
Volume90
Issue number12
DOIs
Publication statusPublished - Dec 1999

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Fujii, K., Miyashita, T., Takanashi, J. I., Sugita, K., Kohno, Y., Nishie, H., Yasumoto, S. I., Furue, M., & Yamada, M. (1999). γ-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells. Japanese Journal of Cancer Research, 90(12), 1351-1357. https://doi.org/10.1111/j.1349-7006.1999.tb00719.x