Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. We studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K- and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. Pituitary adenoma tissue and lymphocytes were obtained from patients at the time of transsphenoidal surgery. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7, and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact in GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients, demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRL-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site.
 ...
PMID:Molecular screening of pituitary adenomas for gene mutations and rearrangements. 810 Aug 31

The term "nonfunctioning" pituitary adenomas (NFPA) implies heterogeneity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual function, and despite the secretion of gonadotropins, hypogonadism is frequent. NFPA must be differentiated from prolactinomas, because of the therapeutic implications, but although prolactin (PRL) levels greater than 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-releasing hormone (GnRH) is of no use, but the thyrotropin-releasing hormone (TRH) test is invaluable. NFPA are monoclonal in origin, but genetic mutations data have not clarified their etiology, which remains largely unknown. Proliferating cell nuclear antigen expression is increased in recurrent adenomas, as is abnormality and overexpression of the protein kinase C family in aggressive tumors. Mutations of tumor-suppressor genes, such as the p53 and Rb genes, and of the metastasizing suppressor gene nm23, have been found in invasive tumors. Immunohistochemistry data confirm that most NFPA originate from gonadotroph cells; many NFPA are negative for all anterior pituitary hormones tested, although isolated or clustered cells are often positive for glycoprotein hormones or their subunits. Silent gonadotroph and also silent growth hormone (GH) or corticotroph tumors can constitute the anatomical basis for clinical NFPA. The heterogeneity of the immunohistochemistry data is reflected in the receptor complex of these tumors. Dopaminergic receptors have recently been visualized in vivo and there are also receptors for TRH or GnRH, since levels of alpha or beta subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, three second-line pharmacological approaches have been tried: dopamine agonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first.
 ...
PMID:Nonfunctioning adenomas of the pituitary. 876 90

An interesting multiple tumor case is described in which 4 different kinds of tumors were diagnosed in the same patient at autopsy and histopathologic examination. The tumors were the following: 1) prolactinoma of the anterior pituitary lobe; 2) basal cell carcinoma of the nose; 3) adenocarcinoma of the colon sigmoideum; 4) multiple oncocytomas (oncocytomatosis) in the kidneys. Immunohistochemical investigation for p53 revealed a strong intranuclear positivity in the colonic carcinoma cells as a result of the overexpression of a possible mutant type of the protein. The other 3 tumors were negative with the p53-specific DO-7 antibody, therefore, no point mutation was thought to be present in the p53 gene of the tumor cells. The immunohistochemical and anamnestic data suggested that this is not a hereditary syndrome, and there is no common pathogenesis of these tumors. Its rarity is interesting in our case because of the coincidence of 4 different unrelated tumors and the absence of anamnestic data for familial accumulation or predisposition for multiple tumors.
 ...
PMID:Multiple tumor case: report and analysis of an autopsy case. 926 95

A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000 mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal surgery and pituitary irradiation, she became increasingly resistant to high doses of bromocriptine and underwent transfrontal surgery followed by stereotactic radiotherapy. In spite of these treatments, serum prolactin estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging scanning demonstrated a massive cystic tumor invading the temporal lobes, extending into the cervical and thoracic spine, with metastases to cervical lymph nodes. High-dose cabergoline administration resulted in a 30% decrease in serum PRL. Octreotide was administered as a continuous sc infusion with a profound analgesic effect on facial pain but with no effect on tumor progression. She was treated with a course of chemotherapy consisting of carboplatin and etoposide without any noticeable effect. The patient died 6 months following chemotherapy. Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb protein, c-myc, and p53 both in the original and metastatic tumors. The metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma remains a therapeutic challenge. It is associated with a variable proto-oncogene expression, which may be coincidental or causal. Cabergoline had no advantage over bromocriptine. Octreotide relieved facial pain but did not alter tumor progression. An effective therapy for metastatic prolactinoma remains to be identified.
 ...
PMID:Metastatic prolactinoma: effect of octreotide, cabergoline, carboplatin and etoposide; immunocytochemical analysis of proto-oncogene expression. 928 27

We reported a case of sarcomatous transformation of pituitary adenoma occurring in a 21-year-old woman. She had previously undergone surgery for pituitary adenoma (prolactinoma) 5 years earlier. Since then, she had received only bromocriptine medication therapy. The operation was repeated because of a relapse of the tumors. Histologically, the tumors were composed of adenomatous epithelial nests and fibrosarcomatous spindle cell components intermingled with each other. lmmunohistochemically, adenomatous epithelial cells were stained positively with cytokeratin and prolactin. Fibrosarcomatous spindle cells were stained only with vimentin. The proliferation activity (Ki-67 expression) was much higher in the sarcomatous components than in common pituitary adenoma. p53 immunostaining was also positive in sarcomatous components. This was thought to be the first reported case of sarcomatous transformation of pituitary adenoma not associated with radiation therapy.
 ...
PMID:Sarcomatous transformation of pituitary adenoma after bromocriptine therapy. 949 Feb 82

Two groups of prolactinomas were identified, one slowly proliferating and responsive to bromocriptine and one fast proliferating and bromocriptine resistant. Nerve growth factor (NGF) inhibits proliferation of bromocriptine-resistant cells by mechanisms that are still unclear. The tumor suppressor p53 is one of the key regulators of cell proliferation and in most tumors, but not pituitary adenomas, it is inactivated by genomic mutations. Here we investigated whether in prolactinoma cell lines NGF influences cell cycle-related pathways involving p53. By using conformation-specific antibodies and immunocytochemistry we found that in bromocriptine-resistant cells p53 adopts a mutant conformation that precludes its nuclear translocation and transcriptional activity. NGF administration to these cells refolds p53 into wild-type tertiary structure, promotes its nuclear translocation, and restores its DNA-binding activity as demonstrated by the transcriptional activation of p21Cip1/WAF1 and the resulting down-regulation of different cyclins and cyclin-dependent kinase 2. Inactivation of trkA, but not of p75NTR, and wortmannin prevented NGF-induced p53 nuclear translocation. Thus, in prolactinoma cells p53 is inactivated by conformational mutation and cytoplasmic segregation. This defect is reversible because NGF reconstitutes active p53 in these cells. This effect of NGF is exclusively mediated by trkA through activation of phosphatidylinositol-3-kinase and may be related to its growth-inhibitory action.
 ...
PMID:Nerve growth factor restores p53 function in pituitary tumor cell lines via trkA-mediated activation of phosphatidylinositol 3-kinase. 1452 55

Pituitary carcinomas are extremely rare. In general, the initial clinical, biochemical, and histological characteristics are of minimal utility in distinguishing benign adenomas from pituitary carcinomas. We describe a 63-year-old woman with a macroprolactinoma, who presented with diplopia and blurred vision. This unusual initial presentation and the subsequent aggressive clinical course, with diffuse local and distant intramedullary metastases, prompted us in retrospect to make a detailed analysis of the therapeutic interventions and histology. In addition, we reviewed all available literature on published cases of malignant prolactinoma and detailed their epidemiological, clinical, and histopathological characteristics. In brief, it is postulated that pituitary carcinomas arise from the transformation of initially large, but benign, adenomas. Unusual and/or atypical clinical manifestations appear to occur more frequently. In vivo, the development of dopamine agonist resistance in invasive macroprolactinoma is indicative of malignancy and should prompt the clinician to perform a biopsy of the tumor. For pituitary tumors that exhibit high mitotic activity, increased Ki-67 and/or p53 immunoreactivity, it may be useful to denote these tumors as 'atypical' prolactinomas to raise the possibility of future malignant development.
 ...
PMID:Malignant prolactinoma: case report and review of the literature. 1699 Jun 51

Prolactinomas are the most common secretory pituitary tumors; however, their pathogenesis is unclear. In order to explore the pathogenesis of prolactinomas, we used fiber-optic BeadArray to examine gene expression profiles in five prolactinomas compared with three normal pituitaries. Three down-regulated genes and one up-regulated gene were chosen for validation by quantitative real-time reverse-transcription polymerase chain reaction. We then performed pathway analysis on the identified differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Array analysis showed significant increases in the expression of 27 genes and 3 expressed sequence tags (ESTs), and decreases in 182 genes and 9 ESTs, including HIG1 domain family, member 1B, S100 calcium binding protein A9, angiopoietin 2, interleukin 8, hydroxyprostaglandin dehydrogenase 15-(NAD), suppression of tumorigenicity18, and WNT inhibitory factor 1. Pathway analysis showed that the P53 and GnRH signaling pathways may play an important role in tumorigenesis of prolactinomas. Our data suggest fiber-optic BeadArray combined with pathway analysis of differential gene expression profile appears to be a valid approach for investigating the pathogenesis of tumors.
 ...
PMID:Analysis of differential gene expression by fiber-optic BeadArray and pathway in prolactinomas. 2097 30

Pituitary carcinomas are rare adenohypophyseal tumors with cerebrospinal or extracranial metastasis. None of the histologic findings distinguish pituitary adenoma from carcinoma. We describe clinico-pathological and immunohistological features of malignant prolactinoma. The patient initially presented with a prolactin-secreting pituitary adenoma. The tumor showed aggressive clinical course presenting with repeated recurrences and eventually metastasized to multiple bones. MIB-1 and p53 labeling indices were also compared in primary adenoma, recurrent invasive adenoma and metastatic tumor.
 ...
PMID:Malignant prolactinoma: a rare case report. 2104 11

The objective of this study was to describe a familial screening for AIP mutations in the context of aggressive prolactinoma in childhood. A 12-year-old boy, presented headaches and bilateral hemianopsia. He had adequate height and weight for his age (50(th) percentile), Tanner stage G1 P1. His bone age was 10 years. Prolactin was 10.560 ng/mL (3-25), FSH and LH were undetectable, IGF-1, TSH, Free T4, ACTH, and cortisol were within normal ranges. MRI showed a pituitary macroadenoma, 5.3 X 4.0 X 3.5 cm with compression of the optic chiasm, bilateral cavernous sinus invasion, encasement of carotids, and extension to clivus. Surgical debulking was performed. Resistance to cabergoline was characterized and he was submitted to two surgeries and radiotherapy. Immunohistochemical evaluation included prolactin, ACTH, GH, FSH, LH,AIP, c-erb B2, Ki-67, and p53. Genomic DNA was isolated from the index case and 48 relatives, PCR and sequencing were performed.A germline A195V mutation in AIP was identified in the index case and in five asymptomatic relatives. Germline mutations in the AIP gene may be involved in the predisposition to pituitary adenoma formation, as cause or co-factor in pathogenesis of aggressive tumors in young patients.
 ...
PMID:Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene. 2134 Jan 66


1 2 Next >>