Open Accessγ‐Irradiation Deregulates Cell Cycle Control and Apoptosis in Nevoid Basal Cell Carcinoma Syndrome‐derived Cells
Author(s) -
Fujii Katsunori,
Miyashita Toshiyuki,
Takanashi Junichi,
Sugita Katsuo,
Kohno Yoichi,
Nishie Haruko,
Yasumoto Shinichiro,
Furue Masutaka,
Yamada Masao
Publication year - 1999
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1999.tb00719.x
Subject(s) - nevoid basal cell carcinoma syndrome , biology , cell cycle , carcinogenesis , apoptosis , pathology , cancer research , basal cell carcinoma , basal cell nevus syndrome , cancer , medicine , genetics , basal cell
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 G 2 M phase after γ‐irradiation, whereas normal cells showed cell cycle arrest both in the G 0 G 1 and G 2 M 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.