Molecular Biology And

Abstract

Alterations in cell survival may contribute to tumour development, influence tumour biology and its response to chemotherapy. Apoptosis may be triggered by p53-dependent or p53-independent mechanisms that share downstream biochemical pathways. P53-dependent apoptosis is stimulus specific. In several cell types wild-type p53 protein is necessary for induction of apoptosis after defects in p53-dependent apoptotic response may contribute to malignant transformation, tumour progression and tumour resistance to DNA damage-inducing therapy. P53-mediated apoptosis involves transcriptional repression of bcl-2, activation of bax and bcl-xL, as well as immediate interaction with proteins – mediators of apoptosis Bcl-2 and bcl-x L proteins are inhibitors of programmed cell death, while bax belongs to promotors. It is suggested that both bcl-2 and bax proteins may participate in mitochondrial pore formation, and thus influence the execution step of apoptosis. Bcl-2 and bcl-x L anti-apoptotic proteins may be blocked by complex formation with bax (Reed, 1997). Little is known on apoptosis regulation in vivo. p53 gene alterations are very frequent in ovarian cancer – they have been found in 81% of serous type tumours in our own material, and are rather an early step in the development of ovarian cancer (Kupryjanczyk et al, 1993, 1995a; reviewed in Kupryjanczyk, 1996). One may expect that p53 gene mutations will negatively influence p53-dependent spontaneous and induced apoptosis. It is assumed that poor response to DNA-damage in tumours bearing a p53 gene mutation may cause genomic instability and tumour progression, as well as resistance to DNA damage-inducing therapy. However, studies on p53 status and response to cisplatin-based chemotherapy have not given so far equivocal results (Righetti et al, 1996; De Feudis et al, 1997). To our knowledge, spontaneous apoptosis has not been evaluated in relation to p53 gene mutation neither in ovarian or other tumour samples. Also, nothing is known about possible prognostic value of spontaneous apoptosis in ovarian Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction Summary Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and …