Garrido C, Fromentin A, Bonnotte B, Favre N, Moutet M, Arrigo A P, Mehlen P, Solary E
Institut National de la Santé et de la Recherche Médicale CJF 94-08, Faculty of Medicine and Pharmacy, Dijon, France.
Cancer Res. 1998 Dec 1;58(23):5495-9.
The REG and PRO cell clones were obtained from a colon adenocarcinoma induced in a BDIX rat by 1,2-dimethylhydrazine. When injected s.c. into syngeneic hosts, REG cells induce tumors that regress in less than 3 weeks, whereas PRO cells, like parental cells, induce progressive tumors. Here, we show that compared to PRO cells, REG cells are more sensitive to cell death induced by anticancer drugs. The small heat shock protein (HSP) 27 is not expressed or inducible in REG clones, whereas it is abundantly expressed and inducible by heat shock in PRO clones. The expression of HSP27 in REG cells increases their resistance to apoptosis in vitro and dramatically enhances their tumorigenicity when injected s.c. into syngeneic rats. HSP27 expression in REG cells both increases tumor size and delays tumor regression. This increased tumorigenicity is associated with a substantial decrease of in vivo tumor cell apoptosis. We conclude that HSP27 expression in malignant cells increases their tumorigenicity in syngeneic animals. In combination with the role of HSP27 in tumor cell resistance to cytotoxic agents, its contribution to tumorigenicity makes this protein a potential target for antitumoral therapy.
REG和PRO细胞克隆是从用1,2 - 二甲基肼诱导BDIX大鼠产生的结肠腺癌中获得的。当将REG细胞皮下注射到同基因宿主中时，会诱导肿瘤在不到3周内消退，而PRO细胞则像亲代细胞一样，诱导肿瘤进行性生长。在此，我们表明，与PRO细胞相比，REG细胞对抗癌药物诱导的细胞死亡更敏感。小热休克蛋白（HSP）27在REG克隆中不表达或不可诱导，而在PRO克隆中大量表达且可被热休克诱导。REG细胞中HSP27的表达增加了它们在体外对凋亡的抗性，并且当皮下注射到同基因大鼠中时显著增强了它们的致瘤性。REG细胞中HSP27的表达既增加了肿瘤大小又延迟了肿瘤消退。这种增加的致瘤性与体内肿瘤细胞凋亡的显著减少相关。我们得出结论，恶性细胞中HSP27的表达增加了它们在同基因动物中的致瘤性。结合HSP27在肿瘤细胞对细胞毒性剂抗性中的作用，其对致瘤性的贡献使这种蛋白质成为抗肿瘤治疗的潜在靶点。
