In order to investigate the role of TP53 in tumour progression and metastasis, we analysed 33 liver metastases of colorectal carcinomas and 19 primary colon carcinomas from the same hospital with respect to mutational changes, loss of heterozygosity and expression of the TP53 tumour suppressor gene.
Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
Mutations in the p53 tumor suppressor gene frequently result in expression of p53 point mutants that accumulate in cancer cells and actively collaborate with tumor progression through the acquisition of novel properties.
Notably, TP53 mutation, which has been used as a marker of tumor progression in many human cancers, was less significant in associating with progression in this study (P = 0.04) than was p16 or pRb alteration (P = 0.001).
It seems that loss of wild-type p53 gene function and consequent p53 overexpression may be involved in early stages of tumor progression while DCC abnormalities are a late event.
Oncogenic stimuli trigger the DNA damage response (DDR) and induction of the alternative reading frame (ARF) tumor suppressor, both of which can activate the p53 pathway and provide intrinsic barriers to tumor progression.
Alterations in p53 represent one of the most common genetic events in patients with invasive urothelial carcinoma and are suggested to be linked to tumor progression, prognosis, and chemosensitivity. p53 possesses various functions, including induction of cell-cycle arrest, apoptosis, DNA repair, and antioxidants; it acts as a killer and a healer.
This study being first of its kind infers p53 to be a possible integral component of the nSBs, which may regulate cellular stress response during cancer progression in the presence of HSF1 and SatIII.
It has been well established that in addition to abrogating the tumor-suppressive function of wild-type p53, mutant p53 gains new functions and actively contributes to various stages of tumor progression.
On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.
Based on our data, the p53 mutation appears to be an uncommon (2%) genetic event in PXA formation and does not appear to be involved in tumor progression.
These data together suggest that SMAR1 is the only known MARBP that delays tumor progression via direct activation and interaction with tumor-suppressor p53.
Increased expression of p53 was associated with tumor progression because it was overexpressed in 45% of the adenomas and 65% of the adenocarcinomas (P<0.05).
Tumor suppressor p53 is frequently deleted or mutated in aggressive and high-grade ovarian cancer, probably aggravating cancer progression and increasing mortality.
In conclusion, although DAP kinase alteration was relatively rare, DAP kinase alteration and/or p53 mutation may associate with tumor progression in soft-tissue LMSs.
Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy.
This review provides a description of various pharmacological approaches tested to activate p53 (both wild-type and mutant) and to assess the effects of activated p53 on neoplastic progression.