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At least 937 records · Page 52Linked to original sources
PubMed2006

A high-throughput loss-of-function screening identifies novel p53 regulators.

The p53 protein is a sequence-specific transcription factor that plays a crucial role in tumor suppression by inducing apoptosis or cell cycle arrest in response to cellular damage. To identify novel proteins involved in the regulation of p53 transcriptional activity we have performed a large scale RNA interference-based screen. We have identified four genes previously unknown to be involved in modulating p53 activity (GAS41, RPS6K4, RUNDC1 and CRMP-2). The interference of each of these four genes resulted in the upregulation of p53 transcriptional activity and, conversely, their overexpression resulted in the inhibition of p53 target promoters and p53-mediated apoptosis. These observations suggest a role for these genes as p53 inhibitors and imply that they may have oncogenic activity.

Apoptosis↗
PubMed1999

FHIT loss of function in human primary breast cancer correlates with advanced stage of the disease.

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumor suppressor gene involved in different tumor types. We have assessed 29 human primary breast carcinomas for both the presence of abnormal FHIT transcripts and the Fhit protein levels as compared with the normal breast epithelium of the same patients. In addition, we have also examined a second retrospective series of 156 consecutive breast carcinomas for the expression of the Fhit protein. In nine (31%) cases of the first series, FHIT transcripts were either aberrant or absent as determined by reverse transcription-PCR, and Fhit protein levels in tumors were low or absent as determined immunohistochemically. In 11 other cases (38%), only normal FHIT transcripts were detected by PCR, paralleled by the reduction or absence of Fhit protein. In the remaining nine cases (31%), the presence of the normal FHIT transcript corresponded to protein levels that were similar in tumor and normal breast epithelia. Thus, alterations in FHIT transcripts were detected in 31% of the patients, but reduction or absence of Fhit protein occurred in 69% of the breast carcinoma samples examined. These data suggest that alteration in Fhit expression in breast carcinomas is a frequent event. Analysis of correlation between Fhit expression and pathological, clinical, and biological parameters in these 29 tumors and in a second retrospective series of 156 consecutive primary breast carcinomas indicated that a decrease or an absence of Fhit protein expression is associated with high proliferation and large tumor size.

Acid Anhydride Hydrolases↗
PubMed2001

[Successful reanimation of facial paralysis with an indirect anastomosis between hypoglossal nerve and facial nerve, without loss of function of the tongue].

OBJECTIVE: To describe the surgical procedure and the results of the indirect hypoglossal-facial nerve anastomosis using a free nerve graft in patients with facial nerve paralysis. This technique leaves the tongue function intact. DESIGN: Prospective study. METHODS: Tongue function was assessed in 39 consecutive patients who underwent this procedure and facial reanimation was assessed in 29 of these patients who had completed at least 24 months follow-up. Facial nerve function was judged using the House-Brackmann (HB) facial nerve grading system. RESULTS: Tongue movements were normal in all operated patients; one patient had mild homolateral atrophy. Initial facial movements occurred on average 7.5 months postoperatively (range 4 to 18 months) in all but one patient. The results were graded HB II in 6 patients (20.9%), HB III in 13 (44.6%), HB IV in 7 (24.1%), HB V in 2 (6.8%) and HB VI in 1 patient (3.4%). Hemifacial synkineses were noticeable but no mass movements or gross hypertonia were observed (as are often present in direct hypoglossal-facial anastomosis). The results of facial reanimation were significantly better in young patients and when a short time interval between paralysis and surgery existed. HB grade II was achieved only if the duration of paralysis was less than 12 months. CONCLUSION: Indirect hypoglossal-facial anastomosis with interposition of a nerve graft allows preservation of tongue function together with good overall facial reanimation, and is therefore to be preferred to the classical direct hypoglossal-facial anastomosis.

Adult↗
PubMed1992

Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.

Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white patches of skin and hair from which melanocytes are completely absent. A similar disorder of the mouse, "dominant white spotting" (W), results from mutations of the c-kit proto-oncogene, which encodes the cellular tyrosine kinase receptor for the mast/stem cell growth factor. We have identified c-kit gene mutations in three patients with piebaldism. A missense substitution (Phe----Leu) at codon 584, within the tyrosine kinase domain, is associated with a severe piebald phenotype, whereas two different frameshifts, within codons 561 and 642, are both associated with a variable and relatively mild piebald phenotype. This is consistent with a possible "dominant negative" effect of missense c-kit polypeptides on the function of the dimeric receptor.

Amino Acid Sequence↗