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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When low concentrations (2-5 mole %) of cis unsaturated free fatty acids (group A) are intercalated into lymphocyte plasma membrane, capping is inhibited. No effect is seen with trans unsaturated or saturated fatty acids (group B). The capping inhibition is reversible with increasing doses of extracellular calcium. Fluorescence photobleaching recovery has shown that the group A free fatty acids do not inhibit the receptor immobilization associated with patch formation, but inhibit the final energy-dependent movement of the patched receptors into a cap. We have also shown that the group A free fatty acids cause a shift in membrane-bound calcium to the lipid phase from probable protein-associated sites. We have incorporated these findings into a model for capping and membrane-cytoskeletal interactions.
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PMID:Model for capping derived from inhibition of surface receptor capping by free fatty acids. 692 36

Sebaceous nevi (SN) are congenital malformations of the skin with the potential to develop into basal cell carcinoma (BCC). To date, the molecular basis for their carcinogenic potential remains unknown. The genetic defect in BCC is known and involves the human homologue of Drosophila patched (PTCH) on chromosome 9q22.3. The objective of this study was to test whether allelic deletion of the PTCH gene could already be detected in SN. Twenty-one paraffin-embedded SN were investigated in this study. Basaloid cells in conjunction with mature sebaceous glands as well as epidermal layer apart from SN were microdissected and subjected to single-step DNA extraction. We performed the analysis with polymorphic markers at 9q22.3 (D9S15, D9S252, D9S287, and D9S303). Of the 20 informative SN, 8 (40%) exhibited loss of heterozygosity at least at one locus. Here, we provide the first evidence of the involvement of the tumor suppressor gene PTCH in SN. Whether PTCH deletion in SN is associated with progression to BCC and/or other appendageal tumors should be addressed in future studies.
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PMID:The sebaceous nevus: a nevus with deletions of the PTCH gene. 1021 87

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.
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PMID:Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells. 1066 53

Syringocystadenoma papilliferum (SP) is a benign tumor most commonly located on the scalp or face, which frequently arises from a nevus sebaceus (NS). Transition of SP to basal cell carcinoma (BCC) and, albeit rarely, to metastatic adenocarcinoma may occur. Allelic deletions of the human homologue of the drosophila patched gene (PTCH) occur in both NS and BCC. To search for genetic changes in SP, a microdissection-based genetic analysis using polymorphic markers at 9q22 (PTCH; D9S15, D9S303, D9S287, D9S252) as well as markers at 9p21 flanking the tumor suppressor gene p16 (IFNA, D9S171) was performed. Glandular epithelium consisting of two rows of cells as well as adjacent normal tissue or inflammatory infiltrates in the stroma, when present, was dissected and subjected to single-step DNA extraction and loss of heterozygosity (LOH) analysis. Two of 10 informative SP cases showed LOH at 9q22 (PTCH). Three of 7 informative SP cases showed allelic deletions at 9p21 (p16). Allelic loss at 9q22 is consistent with the clinical observation of transition of SP to BCC. The finding of frequent allelic loss at 9p21 is unlikely to be related to the rare transition of SP to metastatic adenocarcinoma. Our study supports the hypothesis of a gatekeeper role of the tumor suppressor gene p16 in a variety of benign and malignant tumors, including SP.
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PMID:Syringocystadenoma papilliferum: a study of potential tumor suppressor genes. 1128 1

Nevus sebaceous is a congenital malformation of the skin within which a number of neoplasms showing adnexal differentiation may arise. Recently, deletions in the patched gene region were reported in nevus sebaceous and constitutive activation of the patched-hedgehog signaling pathway was implicated in the development of tumors arising within nevus sebaceous. To substantiate further a role of the patched-hedgehog signaling pathway in secondary tumors arising within nevus sebaceous, we examined 11 nevus sebaceous associated with secondary tumors for loss of heterozygosity of the patched gene region by microsatellite polymerase chain reaction and patched mRNA expression by in situ hybridization. Unexpectedly, however, none of the tumors (including eight trichoblastomas) and nevus sebaceous lesions showed loss of heterozygosity at any polymorphic loci close to the patched gene. Further more, none of the nevus sebaceous lesions and secondary tumors gave detectable signals for patched mRNA. In contrast, four of 11 sporadic basal cell carcinomas, that were examined for comparison, showed loss of heterozygosity at the patched gene locus (p <0.05), and moderate to strong signals for patched mRNA was observed in all seven basal cell carcinoma tumors examined (p <0.0001). Additional investigation by reverse transcription-polymerase chain reaction in four basal cell carcinomas and two nevus sebaceous tumors also showed the expression of Gli-1, another target gene in the patched-hedgehog signaling pathway, in all the basal cell carcinomas samples but not in any of the nevus sebaceous tumors examined. The findings in this study do not support the view that the deregulation of the patched-hedgehog signaling pathway is involved in the pathogenesis of nevus sebaceous and associated tumors, and show that, although morphologically similar, trichoblastomas and basal cell carcinomas have a different molecular pathogenesis.
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PMID:No evidence of deregulated patched-hedgehog signaling pathway in trichoblastomas and other tumors arising within nevus sebaceous. 1188 39

Chronic ulcerative stomatitis protein (CUSP), the most abundant cutaneous isoform of p63, is a p53-related gene essential for epithelial development. CUSP lacks the N-terminal transactivation domain found on other p53 family members and has been shown to inhibit p53 function in vitro. In this study, biopsies of normal skin (21 of 21), benign neoplasms [seborrheic keratosis (3 of 3), acrochordon (2 of 3), and verruca plana (3 of 3)], and squamous cell carcinomas (SCC) (4 of 4) displayed strong nuclear CUSP immuno-reactivity in epidermal cells. In contrast few basal cell carcinomas (BCC) (7 of 27) and sebaceous nevi (1 of 2) displayed this pattern of CUSP immunoreactivity. Thus, biopsies of cutaneous conditions characterized by sonic hedgehog (SHH) pathway dysregulation were more than 86 times as likely to lack CUSP/p63 immunofluorescence as were other cutaneous samples. Adjacent normal-appearing skin from patients with basal cell nevus syndrome (BCNS) (2 of 3) also lacked CUSP immuno-staining. Lastly, a BCC arising in a patched heterozygous mouse also lacked CUSP immuno-staining. Because CUSP mRNA and protein were detected via Northern and Western analysis in BCC samples lacking CUSP immuno-staining, we sequenced the coding region of CUSP from two non-staining BCCs but found no mutations. Therefore, CUSP appears to be present, unmutated, and yet frequently undetectable by immunofluorescence in cutaneous lesions in both humans and mice that are associated with SHH pathway dysregulation (BCCs, BCNS, and nevus sebaceous).
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PMID:CUSP/p63 expression in basal cell carcinoma. 1210 58

The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of chromosome 9q. We present an 11-year-old girl with clinical features consistent with BCNS including bridging of sella turcica, biparietal bossing, downward slanting palpebral fissures, mandible prognathism, pectus excavatum, thumb abnormalities, occult spina bifida at L5-S4, numerous basal cell nevi, and single basal cell carcinoma. Cytogenetic analysis using high-resolution banding techniques and fluorescence in situ hybridization (FISH) revealed interstitial chromosome deletion 9q22.32-q33.2 involving the PTCH gene as a secondary breakage event to a chromosome translocation t(9;17)(q34.1;p11.2)mat. Further FISH studies showed the translocation breakpoint on 9q34.11 maps proximal to ABL, between the BAC clone RP11-88G17 and the LMX1B gene. The latter gene encodes a transcription factor, in which loss of function mutations are responsible for the nail-patella syndrome (NPS, #161200 OMIM). Interestingly, some features of our proband (e.g., bilateral patellar dysplasia and abnormal clavicular shape), as well as her healthy sister who carries the same translocation, are also found in patients with NPS. The chromosome 17p11.2 breakpoint maps in the Smith-Magenis syndrome common deletion region, within two overlapping BAC clones, CTD-2354J3 and RP11-311F12.
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PMID:Interstitial deletion 9q22.32-q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and features of Nail-Patella syndrome. 1469 18

Nevoid basal cell carcinoma syndrome (NBCCS, basal cell naevus syndrome, Gorlin syndrome) is an autosomal dominant disorder, caused by mutations in the PTCH gene mapped to chromosome 9q22.3. It is characterised by multiple basal cell carcinomas, keratocysts of the jaws, palmar and plantar pits, cerebral ectopic calcification and several skeletal anomalies. Occasionally, patients with NBCCS develop other neoplasms, particularly medulloblastomas and ovarian fibromas, indicating that the PTCH gene is a tumor-suppressor gene. Early recognition and careful follow-up are needed. Guidelines for managing these patients are presented.
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PMID:[From gene to disease: basal cell naevus syndrome]. 1568 38

Germline mutations in the human homolog of the patched1 (PTCH1) are associated with basal cell nevus carcinoma syndrome (BCNS or Gorlin syndrome), which is characterized by developmental anomalies, radiation hypersensitivity and a predisposition to medulloblastomas and skin tumors. Patched1 (Ptc1) functions as a receptor for Sonic hedgehog (Shh) in a wide range of biological processes. Binding of Shh to Ptc1 results in activation of Smoothened (Smo), which in turn stimulates expression of downstream target genes including Ptc1 and Gli1. Gli1 is a member of a family of DNA-binding zinc-finger proteins, including Gli2 and Gli3, that function in transcription control. Here, we report that inactivation of both Gli1 alleles in Ptc1+/- mice significantly reduces spontaneous medulloblastoma formation. Therefore, Gli1 is not only a marker of pathway activation but also plays a functional role in medulloblastoma formation. Interestingly, Gli2 levels were elevated in medulloblastoma cells but not in normal granule neuron precursors during cerebellar development in mice lacking Gli1. In cultured fibroblasts, Gli1 was more potent than Gli2 at inducing cell transformation. These results demonstrate that Gli1 plays a central role in medulloblastoma formation in Ptc1+/- mice and that Gli2 may also contribute to oncogenesis.
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PMID:Gli1 is important for medulloblastoma formation in Ptc1+/- mice. 1580 68

Different physicochemical properties of Langmuir films (monolayers) composed of 10 mixed systems of a bile acid, deoxycholic acid (DC) with various plant sterols, such as stigmasterol (Stig), beta-sitosterol (Sito) and campesterol (Camp) and a stanol, cholestanol (Chsta) in addition to an animal sterol, cholesterol (Ch) [these sterols and Chsta are abbreviated as St] and DC with 1:1 St mixtures; (Ch+Chsta), (Ch+Stig), (Stig+Chsta), (Ch+Sito) and (Ch+Camp) on the substrate of 5M aqueous NaCl solution (pH 1.2) at 25 degrees C, were investigated in terms of mean surface area per molecule (A(m)), the partial molecular area (PMA), surface excess Gibbs energy (DeltaG((ex))), interaction parameter (I(p)) as well as activity coefficients (f(1) and f(2)) in 2-D phase of each binary (or ternary) component system and elasticity (Cs(-1)) of formed films; these were analyzed on the basis of the respective surface pressure (pi) versus A(m) isotherms as a function of mole fraction of Sts (X(st)) in the DC/St(s) mixtures at discrete surface pressures. Notable findings are: (i) all the binary component systems did form patched film type monolayers consisting of (a) DC-dominant film solubilizing a trace amount of St molecules and (b) St dominant film dissolving a small amount of DC molecules, (ii) DC in 2-D phase exhibited a transition from LE film to LC film at a constant pressure (pi(C)(1)) accompanied by compression and (iii) DeltaG((ex)) as well as I(p) was found to be greatly dependent on (a) the combinations of DC with different St species and (b) to be markedly varied by a difference in mixing ratio of DC to Sts. Compressibility (or elasticity) analyses and fluorescence microscopy images could support the above findings as well as interpretation.
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PMID:Monolayers (Langmuir films) behavior of multi-component systems composed of a bile acid with different sterols and with their 1:1 mixtures. 1748 1


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