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Biomedical subjects

A Nadal

Publications and source records attributed to A Nadal.

At least 37 records · Page 2Linked to original sources
PubMed1999

Disregulation of p16MTS1/CDK4I protein and mRNA expression is associated with gene alterations in squamous-cell carcinoma of the larynx.

To determine the relationship between p16MTS1/CDK4I expression, gene inactivation and 9p21 loss of heterozygosity (LOH) in the development of laryngeal carcinomas, we have examined p16MTS1/CDK4I protein and mRNA expression in a series of 7 normal and 36 tumoral tissues, and the presence of gene alterations and 9p21 LOH. Fifteen tumors (42%) showed low levels of pl6MTS1/CDK4I protein expression (similar to normal samples), 7 carcinomas (19%) expressed higher levels, and no protein expression was seen in 14 tumors (39%). No gene alterations were detected in 11 of the 15 tumors (73%) with protein levels similar to normal tissues. Most of the cases with absence of protein expression (86%) had gene alterations. Of the 7 tumors with protein over-expression, 4 showed frameshift or point mutations (2 cases each). mRNA analysis showed pl6MTS1/CDK4I -gene expression in 12 of 17 carcinomas examined. Gene alterations were detected in 9 of the 12 mRNA-positive tumors and in 2 of the 5 negative carcinomas. Concordant expression of p16alpha and p16beta transcripts was observed in all tumors. 9p21 LOH was detected in 23 carcinomas, 18 of which (78%) showed associated p16MTS1/CDK4I -gene alterations. These results indicate that disregulation of p16MTS1/CDK4I protein and mRNA expression is a frequent phenomenon in laryngeal carcinomas commonly associated with gene alterations and 9p21 LOH. The relative number of discrepancies between protein and mRNA expression and the presence of genetic alterations indicate that a comprehensive study of the gene including all these parameters may be necessary to assess the role of this gene in the pathogenesis of such tumors.

Amino Acid Substitution↗
PubMed1999

Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse.

1. Using laser scanning confocal microscopy to image [Ca2+]i within intact murine islets of Langerhans, we analysed the [Ca2+]i signals generated by glucose in immunocytochemically identified alpha-, beta- and delta-cells. 2. Glucagon-containing alpha-cells exhibited [Ca2+]i oscillations in the absence of glucose, which petered out when islets were exposed to high glucose concentrations. 3. Somatostatin-containing delta-cells were silent in the absence of glucose but concentrations of glucose as low as 3 mM elicited oscillations. 4. In pancreatic beta-cells, a characteristic oscillatory calcium pattern was evoked when glucose levels were raised from 3 to 11 mM and this was synchronized throughout the beta-cell population. Remarkably, [Ca2+]i oscillations in non-beta-cells were completely asynchronous, both with respect to each other and to beta-cells. 5. These results demonstrate that the islet of Langerhans behaves as a functional syncytium only in terms of beta-cells, implying a pulsatile secretion of insulin. However, the lack of a co-ordinated calcium signal in alpha- and delta-cells implies that each cell acts as an independent functional unit and the concerted activity of these units results in a smoothly graded secretion of glucagon and somatostatin. Understanding the calcium signals underlying glucagon and somatostatin secretion may be of importance in the treatment of non-insulin-dependent diabetes mellitus since both glucagon and somatostatin appear to regulate insulin release in a paracrine fashion.

Animals↗
PubMed1999

Expression of p27/Kip1 is down-regulated in human prostate carcinoma progression.

p27(Kip1) is a cyclin-dependent kinase inhibitor whose down-regulation has been observed in several tumour models, including breast, colorectal, and gastric carcinomas. The purpose of this study was to assess p27(Kip1) protein expression in normal and benign prostatic epithelia as well as the possible existence of abnormalities in prostate carcinoma progression. p27(Kip1) expression was immunohistochemically analysed in 51 normal tissue samples, 11 nodular hyperplasias (NH), 22 high-grade prostatic intraepithelial neoplasias (PIN), 56 localized prostate adenocarcinomas, and 19 metastases. Immunoblotting was performed in ten cases. Normal prostate epithelium and NH showed diffuse and intense p27(Kip1) nuclear expression in most cases. A significant p27(Kip1) down-regulation was observed in many carcinomas when compared with benign epithelium. Forty-seven cases (84 per cent) were low p27(Kip1) expressors (<50 per cent positive cells) and nine cases (16 per cent) were high p27(Kip1) expressors. p27(Kip1) down-regulation was also consistently seen in PIN. Fourteen out of 19 metastases (74 per cent) were low p27(Kip1) expressors. Six metastatic samples had their corresponding primary tumour analysed and three cases showed decreased expression in the metastasis. It is concluded that p27(Kip1) is constitutively expressed in normal and benign prostatic tissue. This expression is clearly down-regulated in neoplastic progression from the preinvasive lesions through invasive carcinoma and metastases and this therefore occurs in early stages of neoplastic transformation.

Adenocarcinoma↗
PubMed1999

c-myc mRNA expression and genomic alterations in mantle cell lymphomas and other nodal non-Hodgkin's lymphomas.

Cyclin D1 is a weak oncogene that cooperates with c-myc activation in the development of B cell lymphomas in transgenic animals. Cyclin D1 is constantly overexpressed in human mantle cell lymphomas (MCL). However, the status of c-myc gene in these tumors is not known. We have examined the c-myc mRNA expression and genomic alterations, including mutational analysis of exon 1, intron 1, and exon 2 regulatory elements, in a series of 33 MCL, 22 typical and 11 blastoid variants. In addition, c-myc alterations were also examined in 56 nodal non-Hodgkin's lymphomas (NHL). c-myc mRNA overexpression was found in 38% (11/29) of MCL with a slightly higher frequency in blastoid variants (5/10, 50%) than in typical cases (6/19, 31%). Genetic alterations were only found in one blastoid MCL showing a three-fold c-myc gene amplification. In other nodal NHL, c-myc overexpression was found in 24% (7/29) of indolent tumors but in 70% (19/27) of aggressive variants. c-myc Genetic alterations detected in these cases were gene rearrangement and hypermutations in one Burkitt's lymphoma, and individual point mutations in intron 1 or exon 2 in 1/19 (5%) indolent and 7/16 (44%) aggressive variants. These results indicate that c-myc is overexpressed in a subset of MCL, but structural gene alterations are less frequent than in other nodal NHL.

Blotting, Southern↗
PubMed1999

Different effects of tolbutamide and diazoxide in alpha, beta-, and delta-cells within intact islets of Langerhans.

Interaction between the different types of cells within the islet of Langerhans is vital for adequate control of insulin release. Once insulin secretion becomes defective, as in type 2 diabetes, the most useful drugs to increase insulin release are sulfonylureas. It is well-known that sulfonylureas block K(ATP) channels, which results in depolarization of the membrane that provokes calcium influx and increases intracellular calcium concentration ([Ca2+]i), which thereby triggers insulin secretion. The sulfonamide diazoxide produces the opposite effect: it activates K(ATP) channels, resulting in a decreased insulin secretion. Despite such evidence, little is known about the effect of sulfonylureas and sulfonamides in non-beta-cells of the islet of Langerhans. In this article, we describe the effects of tolbutamide and diazoxide on [Ca2+]i in alpha-, beta-, and delta-cells within intact islets of Langerhans. Tolbutamide elicits an increase in [Ca2+li in beta- and delta-cells, regardless of glucose concentrations. Remarkably, tolbutamide is without effect in alpha-cells. When diazoxide is applied, glucose-induced [Ca2+]i oscillations in beta- and delta-cells are abolished, whereas [Ca2+]i oscillations in alpha-cells remain unaltered. Furthermore, the existence of sulfonylurea receptors is demonstrated in beta-cells but not in alpha-cells by using binding of glybenclamide-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) combined with immunostaining for insulin and glucagon.

Animals↗
PubMed1999

Effects of hexose pentaacetates on electrical activity and cytosolic Ca2+ in mouse pancreatic islets.

Electrical activity of beta-cells and cytosolic Ca2+ concentration ([Ca2+]i) were monitored in mouse pancreatic islets exposed to the pentaacetate esters of alpha-D-glucose, beta-D-galactose and beta-L-glucose, all tested at 1.7 mM concentration. In the presence of 5 mM D-glucose, alpha-D-glucose pentaacetate induced electrical activity and increased [Ca2+]i, whilst beta-D-galactose pentaacetate failed to do so. The electrical and cationic response to the D-glucose ester occurred with a delay of between 5 and 10 min, the ester-induced increase in [Ca2+]i being suppressed in the absence of extracellular Ca2+. As a rule, beta-L-glucose pentaacetate also failed to evoke biophysical responses in the islets exposed to 5 mM D-glucose. However, in the presence of 10 mM L-leucine the L-glucose ester induced electrical activity. These findings, which parallel the insulinotropic action of the same esters in rat pancreatic islets reinforce the view that the positive insulinotropic action of selected hexose pentaacetates cannot be attributed to the catabolism of their acetate moiety but, instead, involves a dual mode of action linked to both the metabolism of their carbohydrate moiety and a direct effect of the ester itself upon a yet unidentified receptor system. Furthermore, this study provides the first evidence that the latter direct effect results in the induction of both electrical activity and [Ca2+]i oscillations.

Animals↗
PubMed1999

Lysophospholipids trigger calcium signals but not DNA synthesis in cortical astrocytes.

Astrocytes generate calcium signals and proliferate in response to a growth factor-like lipid bound to plasma and serum albumin, in a process likely to be important in the formation of glial scars. A number of potential candidates for the physiologically active lipid were investigated. Lysophosphatidic acid, lysophosphatidylcholine, sphingomyelin, and platelet-activating factor all elicited calcium signals of varying magnitudes in cortical astrocytes, although only lysophosphatidic acid elicited calcium signals comparable in amplitude to those induced by the active physiological lipid. None of these lipids, however, caused cell division in astrocytes. There is therefore no invariable relationship between the ability of lipids to induce calcium signals and mitogenic activity. None of the lipids investigated demonstrate the activity of the natural lipid factor in generating both calcium signals and mitotic activity in astrocytes.

Animals↗
PubMed1998

Albumin elicits calcium signals from astrocytes in brain slices from neonatal rat cortex.

1. Albumin causes calcium signals and mitosis in cultured astrocytes, but it has not been established whether astrocytes in intact brain also respond to albumin. The effect of albumin on intracellular calcium concentration ([Ca2+]i) in single cells was therefore studied in acutely isolated cortical brain slices from the neonatal rat. 2. Physiological concentrations of albumin from plasma and from serum produced an increase in [Ca2+]i in a subpopulation of cortical cells. Trains of transient elevations in [Ca2+]i (Ca2+ spikes) were seen in 41 % of these cells. 3. The cells responding to albumin are identified as astrocytes because the neurone-specific agonist NMDA caused much smaller and slower responses in these cells. On the other hand NMDA-responsive cells, which are probably neurones, exhibited only small and slow responses to albumin. The residual responses of astrocytes to NMDA and neurones to albumin are likely to be due to crosstalk with adjacent neurones and astrocytes, respectively. 4. Methanol extraction of albumin removes a polar lipid and abolishes the ability of albumin to increase intracellular calcium. 5. Astrocyte calcium signalling caused by albumin may have important physiological consequences when the blood-brain barrier breaks down and allows albumin to enter the CNS.

Albumins↗
PubMed1998

cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.

cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.

Blotting, Northern↗
PubMed1998

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.

p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.

Blotting, Western↗
PubMed1998

Collagenase-3 expression is associated with advanced local invasion in human squamous cell carcinomas of the larynx.

Collagenase-3 (MMP-13) is a matrix metalloproteinase recently identified on the basis of differential expression in normal breast tissues and in breast carcinoma. To date, collagenase-3 expression has been reported only in breast carcinomas and in articular cartilage of arthritic patients; the presence and possible implication of this enzyme in the progression of other malignant tumours are unknown. In this study collagenase-3 mRNA expression has been analysed by northern blot in a series of 35 matched squamous cell carcinomas of the larynx and the corresponding adjacent non-neoplastic tissues. In addition, mRNA expression of membrane type 1-matrix metalloproteinase (MT1-MMP) and gelatinase A, two matrix metalloproteinases which have the ability to activate collagenase-3 in vitro, was also examined in the same cases. No collagenase-3 expression was detected in any of the 35 normal mucosae, but collagenase-3 mRNA was observed in 20 of the 35 carcinomas (57 per cent). Western blot analysis revealed the presence of collagenase-3 protein in those carcinomas with high levels of mRNA expression, whereas no protein was detected in the carcinomas with negative mRNA expression, or in any of the normal tissues. The protein was localized predominantly in tumour epithelial cells. Collagenase-3 expression correlated significantly with better histological differentiation of the tumours (p = 0.026), as well as with advanced local invasion (p = 0.026). Collagenase-3 upregulation was also significantly associated with MT1-MMP and gelatinase A overexpression. These findings suggest that collagenase-3 expression may contribute to the progression of a significant subset of squamous cell carcinomas of the larynx and that its coordinate overexpression with MT1-MMP and gelatinase A may have a cooperative effect in the progression of the tumours.

Adult↗
PubMed1998

Cancer dissemination during laparoscopic surgery: tubes, gas, and cells.

Port-site metastasis has been an unexpected finding after laparoscopic surgery in gastrointestinal cancer patients. No clear explanation exists for this phenomenom. The aims of this study were to evaluate the dissemination pattern in an experimental model of hepatocarcinoma in the rat and summarize current knowledge about the risks and the results of experimental studies on cancer dissemination during laparoscopic surgery. NDA-induced hepatocarcinoma was obtained in Sprague-Dawley rats. Tumors were manipulated during laparoscopy (group 1, n = 11) or laparotomy (group 2, n = 12). A Medline review of all experimental studies about the risk of cancer dissemination during laparoscopic surgery was undertaken. Both models were associated with implants in parietal wounds [1/11 in group 1 (9%) vs. 1/12 in group 2 (8%), p = NS]. Analysis of the current literature confirms that laparoscopy is associated with abdominal cell mobilization, and cells can be recovered in trocars, filtered exhaust gas, and instruments. Postoperative immunosuppression, the biologic aggressiveness of the tumor, and the gas used for laparoscopy also influence tumoral growth. Port-site metastases are secondary to multiple factors, including the technical skill of the surgeon, the biologic properties of the tumors, and local environmental aspects. Undoubtedly, laparoscopy can help disseminate aggressive tumors and should be reserved for diagnostic and staging procedures or for treatment of low-grade malignant tumors. Therapeutic resection, especially of colon cancer, should be restricted to prospective and randomized trials until there are enough hard data to rule out the clinical importance of this potentially severe complication.

Animals↗
PubMed1998

Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor.

Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Although a clear demonstration of a direct effect of 17beta-estradiol on the pancreatic ss-cell is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17beta-estradiol in mouse pancreatic ss-cells. 17beta-Estradiol, at physiological concentrations, closes K(ATP) channels, which are also targets for antidiabetic sulfonylureas, in a rapid and reversible manner. Furthermore, in synergy with glucose, 17beta-estradiol depolarizes the plasma membrane, eliciting electrical activity and intracellular calcium signals, which in turn enhance insulin secretion. These effects occur through a receptor located at the plasma membrane, distinct from the classic cytosolic estrogen receptor. Specific competitive binding and localization of 17beta-estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17beta-estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM. receptor.

ATP-Binding Cassette Transporters↗
PubMed1997

Actions of serum and plasma albumin on intracellular Ca2+ in human endothelial cells.

1. The effects of serum and plasma albumin on [Ca2+]i in human endothelial cells were examined using single-cell Ca2+ imaging. Two types of endothelial cell were used: human umbilical vein endothelial cells (HUVEC) in primary culture, and the endothelial-derived cell line ECV304. 2. Serum albumin caused a large and transient rise in [Ca2+]i, due to Ca2+ release from an IP3-sensitive internal store, followed by a maintained elevation in [Ca2+]i attributable to Ca2+ influx from the external medium. A half-maximal rise in [Ca2+]i was produced by a concentration of serum albumin of about 1 microgram ml-1. 3. The Ca(2+)-releasing action of serum albumin is abolished by methanol extraction and is therefore attributable to an attached polar lipid. A possible candidate is lysophosphatidic acid, known to be released from platelets during blood coagulation, which produced similar effects to those of serum albumin. 4. In HUVEC, plasma albumin caused a sustained decrease in [Ca2+]i from the mean resting level of 114 nM to 58 nM. No effect of plasma albumin was observed in ECV304 cells. 5. The decrease in [Ca2+]i caused by plasma albumin is due to an uptake into intracellular stores. The store loading substantially potentiates the action of Ca(2+)-releasing agonists such as histamine. 6. The results show that normal plasma albumin, which carries few lipids, lowers [Ca2+]i and potentiates the actions of Ca(2+)-releasing agonists by promoting Ca2+ uptake into intracellular stores. When converted to the serum form, by binding lysophosphatidic acid released during blood coagulation, albumin has a potent effect in elevating [Ca2+]i. Blood coagulation may therefore play a role in regulating vascular tone and capillary permeability.

Calcium↗
PubMed1997

p16MTS1/CDK4I mutations and concomitant loss of heterozygosity at 9p21-23 are frequent events in squamous cell carcinoma of the larynx.

We have examined the presence of p16MTS1/CDK4I gene deletions, mutations and methylation status, and 9p21-23 deletions in a series of 46 squamous cell carcinomas of the larynx and paired normal mucosa previously characterized for cyclin D1 gene amplification and overexpression. pRb expression was also examined by immunohistochemistry. p16MTS1/CDK4I mutations were found in 10/46 (22%) carcinomas and hypermethylation in 2/31 (7%). Loss of heterozygosity at 9p21-23 was found in 24 out of 42 (57%) carcinomas examined. All p16MTS1/CDK4I mutated cases and the two hypermethylated carcinomas showed 9p21-23 loss of heterozygosity. The loss of heterozygosity correlated with advanced local invasion (P=0.0045), lymph node metastases (P=0.0326), stage IV of the tumors (P=0.0058), and existence of cyclin D1 amplification/overexpression (P < 0.03). Only one out of 37 carcinomas was negative for pRb expression. No alterations in p16 gene or 9p21-23 loss of heterozygosity were detected in this case. These findings indicate that p16MTS1/CDK4I is frequently inactivated by gene mutation, hypermethylation, and allelic deletions in a significant subset of squamous cell carcinomas of larynx. Since 9p21-23 loss of heterozygosity was more frequently detected than p16MTS1/CDK4I mutations, and mutated carcinomas invariably had loss of heterozygosity, allelic losses probably precede the p16MTS1/CDK4I mutations. Their association with cyclin D1 deregulation in advanced carcinomas could indicate a possible cooperative effect in the progression of these neoplasms.

Aged↗
PubMed1997

Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.

Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically, Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities.

Blotting, Northern↗
PubMed1997

p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx.

p21WAF1/Cip1 is a recently identified gene involved in cell cycle regulation through cyclin-CDK-complex inhibition. The expression of this gene in several cell lines seems to be induced by wild-type, but not mutant, p53. p21WAF1/Cip1 expression has been studied at both mRNA and protein levels in a series of 49 normal mucosae and squamous cell carcinomas of the larynx. A significant association was found between mRNA and protein expression in tumours (P < 0.0001). p21WAF1/Cip1 expression was strongly associated with squamous cell differentiation of carcinomas, because six of seven (86 per cent) undifferentiated carcinomas (grade 4) showed very low levels of p21WAF1/Cip1 expression, whereas 41 out of 42 (98 per cent) carcinomas with squamous cell differentiation (grades 1-3) had normal or high levels of p21WAF1/Cip1 expression (P < 0.0001). In addition, p21WAF1/Cip1 expression was topologically related to the squamous differentiation of tumour cells with a distribution similar to that seen in normal squamous epithelium. No correlation was found between p21WAF1/Cip1 expression and the global S-phase of the carcinomas. p53 mutations (exons 5-9) were found in ten carcinomas with p21WAF1/Cip1 expression, but no p53 mutations were detected in three p21WAF1/Cip1-negative tumours. In conclusion, p21WAF1/Cip1 expression is frequently upregulated in squamous cell carcinomas of the larynx and is associated with tumour cell differentiation. p21WAF1/Cip1 expression in these tumours is independent of p53 gene mutations.

Adult↗