Masanobu Shindoh

Induction of apoptosis by the p53‐273L (Arg→Leu) mutant in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax

Codon 273 is one of the hot spots of missense mutation of the p53 tumor suppressor gene found in human cancers. We have previously reported that a mutation at codon 273, p53‐273L (Arg→Leu), suppresses cell growth despite its having no p53‐specific transactivation activity. To further elucidate the mechanism of growth suppression caused by p53‐273L, we used squamous cell carcinoma cell line HSC3 to isolate subclones containing Zn2+‐inducible wild‐type (wt) p53, p53‐175H, and p53‐273L. Northern blot hybridization of the HSC3 cells possessing an inducible function of p53 as well as a luciferase assay for the p21Waf1/Cip1/Sdi1 promoter showed that only wt p53 could induce p21Waf1/Cip1/Sdi1 transcription. Meanwhile, the expression of bax remained unchanged between, before, and after the induction of any analyzed p53s. When wt p53 was induced in HSC3 cells cultured in medium containing 5% fetal bovine serum, cell growth was suppressed through G1 arrest. On the other hand, in medium with 0.1% fetal bovine serum, the growth of HSC3 cells expressing p53‐273L was suppressed to a greater degree than that of cells expressing wt p53. Flow cytometric analysis and DNA ladder formation revealed that, unlike wt p53‐SN3– and p53‐175H–expressing HSC3 cells, p53‐273L–expressing cells contained a larger sub‐G1 fraction under this culture condition. These findings suggest that p53‐273L can induce apoptosis in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax. Mol. Carcinog. 26:44–52, 1999.

Predominant expression of the src homology 2-containing tyrosine phosphatase protein SHP2 in vascular smooth muscle cells

Abstractsrc homology 2 (SH2)-containing protein-tyrosine phosphatase SHP2 is known to transduce positive signals from activated receptor protein-tyrosine kinases such as platelet-derived growth factor receptor (PDGFR) β and insulin receptor. Here, we demonstrate the physiological expression of SHP2 in rats. In northern and western blot analyses, SHP2 expressions were recognized in all tissues, but their expression levels varied significantly among tissues; it is lowest in the liver and kidney. Immunohistochemical staining and in situ hybridization showed SHP2 was expressed ubiquitously but predominantly in vascular smooth muscle cells (SMC). During the development of granulations, SHP2 was expressed predominantly in vascular SMC and also highly expressed in capillary cells. The functional associations of SHP2 with PDGFRβ, which transduces major growth signals in vascular SMC, identify a crucial function of SHP2 in blood vessels in consert with PDGFRβ.

A case of maxillary sinus origined malignant hemangiopericytoma.

71歳女性に見られた希な上顎洞原発の悪性血管周皮腫例を報告した。腫瘍は歯槽突起, 上顎骨, 頬骨, 眼窩底を破壊して翼口蓋窩に及んでいた。上顎半側切除術ならびにチタンメッシュトレーと前腕皮弁を用いた眼窩底再建術, 60Coによる術後照射 (65Gy/26f) を行った。局所療法終了後にADM, IFO, Mesnaによる補助化学療法を2コース施行した。局所制御が得られたものの, 肺や胸椎に遠隔転移が認められた。