liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Over-expression of coronin 2a and lack of alterations in transforming growth factor ß receptor I in squamous cell carsinomas of the skin
Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
Karolinska Intitute, Department of Biosciences at Novum, Center for Nutrition and Toxicology, Huddinge, Sweden and Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
Karolinska Institute, Department of Biosciences at Novum, Center for Nutrition and Toxicology, Huddinge, Sweden.
Visa övriga samt affilieringar
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

Allelic losses in several regions of chromosome 9q have been connected to the development of squamous cell carcinoma (SCC) of the skin. We have studied two candidate genes in the 9q22 region using mutational analysis of genomic DNA as well as immunohistochemistry for assessment of changes in protein expression. The coronin 2A (CORO2A) protein shows strong resemblance to actin-binding proteins, implying a role in cytokinesis or cell motility. It has also been found to be part of the nuclear receptor co-repressor complex involved in transcriptional regulation. We elucidated the exon-intron structure by sequence alignment of the mRNA to a "high-throughput genomic sequence" entry in GenBank. By using single strand conformation analysis and DNA sequencing we found eight silent mutations in tumor DNA, one of which was found in a subset of a normal control population. Surprisingly, immunostaining revealed over-expression in 4/40 tumors. This cannot explain the high frequency of allelic loss in cutaneous secs, but is yet indicating a possible involvement of CORO2A in cutaneous SCC development. The gene for transforming growth factor ß receptor 1 (TßR-I) has previously been positioned to the 9q22 region. TßR-I is part of a protein complex necessary for binding of the TGFß ligand initiating a signaling cascade, which affects downstream targets important for cell cycle regulation. We could not identify any alterations at either protein or DNA level and therefore exclude TßR-I as candidate for cutaneous sec development.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-85099OAI: oai:DiVA.org:liu-85099DiVA, id: diva2:564574
Tillgänglig från: 2012-11-02 Skapad: 2012-11-02 Senast uppdaterad: 2021-12-28
Ingår i avhandling
1. Molecular alterations in squamous cell carcinomas of the skin: emphasis on genes on chromosome 9q
Öppna denna publikation i ny flik eller fönster >>Molecular alterations in squamous cell carcinomas of the skin: emphasis on genes on chromosome 9q
2004 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Skin cancer is the most common type of cancer in the western world. The incidence of melanoma and non-melanoma skin cancer is continuously increasing and, in Sweden, 2300 new cases per year are diagnosed of squamous cell carcinoma (SCC) alone. In this thesis, we have investigated genes and proteins from signal transduction pathways important for tumor development. Special emphasis has been put on chromosomal region 9q22-q31 where frequent loss of heterozygosity has been observed in non-melanoma skin cancers.

Mutation analysis of the PTCH1 and XPA genes, connected to the familial cancer syndromes nevoid basal cell carcinoma syndrome and xeroderma pigmentosum, respectively, was performed. Based on lack of mutation or altered mRNA expression, we conclude that these two genes are not likely to be involved in development of sporadic SCCs. Next, we studied the correlation of the two phenotypes, anchorage independence and tumorigenicity, to the loss of chromosome 9 material in a panel of somatic cell hybrids. By microsatellite analysis, we show that the anchorage independence gene is located distal to the marker D9S155. The mapping of the gene for tumor suppression revealed three commonly deleted regions on chromosome regions 9p23-p22, 9p21-p12 and 9q31-q33. Another two candidates from the 9q22-q31 region, CORO2A and TßR-I, were investigated both at the gene and the protein level. We did not detect any alterations in the TßR-I gene or protein, but CORO2A protein was over-expressed in 4 of 40 (10%) tumors, indicating an involvement in sec carcinogenesis in a subset of tumors. In one healthy individual from the control population, we found a heterozygous germline mutation in CORO2A creating a stop codon, which results in a truncated protein. Thus, one functional allele might be sufficient to sustain a normal cellular function. When investigating occurrence of aberrant protein expression in the interconnected Wnt and Notch pathways, Notch1 was found to be expressed in only 5 of 40 (14%) of the normal epidermal cells, while strong staining was displayed in all the tumors. No altered expression of the most central protein of the Wnt pathway, ß-catenin, was observed, but the up-stream Dvl-1 protein was found to be up-regulated in 8 of 38 (21%) tumors. Dvl-1 was also detected in the nucleus in the majority of normal and tumor cases and a potential nuclear localization signal was identified in the Dvl-1 A isoform.

None of the genes from the chromosomal region 9q22-q31 displayed alterations consistent with those of a tumor suppressor gene. Most likely, this gene remains to be identified.

Ort, förlag, år, upplaga, sidor
Linköping: Linköpings universitet, 2004. s. 78
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 850
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-23974 (URN)3525 (Lokalt ID)91-7373-823-9 (ISBN)3525 (Arkivnummer)3525 (OAI)
Disputation
2004-05-19, Elsa Brändström-salen, Hälsouniversitetet, Linköping, 13:00 (Svenska)
Opponent
Tillgänglig från: 2009-10-07 Skapad: 2009-10-07 Senast uppdaterad: 2012-11-02Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Person

Eklund, Lena K.Söderkvist, Peter

Sök vidare i DiVA

Av författaren/redaktören
Eklund, Lena K.Söderkvist, Peter
Av organisationen
CellbiologiHälsouniversitetet
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 703 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf