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Laminin-5:function of the γ2 chain in epithelial cell adhesion and migration, and expression in epithelial cells and carcinomasSalo, S. (Sirpa) 31 August 1999 (has links)
Abstract
Laminins are basement membrane glycoproteins consisting of
three polypeptide chains α, β and γ.
Until now 12 members of the protein family have been characterized
and all isoforms have an αβγ chain composition,
but they assemble in varying combinations of chain variants. The
functional properties of laminins include cell adhesion, proliferation,
differentiation, growth and migration. Laminin-5 has a chain composition
of α3β3γ2 with the distribution mainly
restricted to epithelial basement membranes, where its biological
functions involve anchorage and locomotion of cells. The importance
of this protein for the attachment of basal keratinocytes is clearly
demonstrated by the fact that all genes encoding its chains have
been shown to be mutated in the severe skin blistering disease
Epidermolysis bullosa junctionalis.
The present study focused on investigations of the role of
the laminin-5 isoform and particularly its γ2 chain in
cell adhesion and migration. The role of the short arm of the laminin γ2
chain in the process of epithelial cell attachment is to serve
as a kind of a bridging molecule to the extracellular environment,
because it does not have any cell binding activity by itself. It
was also shown that the newly synthesized γ2 chain participates
in the complex process of cell migration, probably as one of the
first attachment components for moving cells. Thus, as a migration
and differentiation-associated molecule, laminin-5 was considered
a potential marker for detection of malignant processes where cell
movement plays a role. Subsequently it was shown that the γ2
chain is expressed not only in a restricted manner in human epithelial
tissues, but also in a number of human epithelium-derived cancers.
In some carcinomas, expression of the γ2 chain appeared
to be a characteristic of cancer cells with invasive properties.
Examination of over 50 dysplasias and cervical tumors revealed
that γ2 chain antibodies were able to distinguish between
lesions with or without invasive capacity. This is the first systematic
study of epithelial cancers where γ2 chain antibodies
have been shown to be a useful marker in the histopathological
diagnostics. In addition, this study showed in a mouse tumor model
that the γ2 chain of laminin-5 has a potential for being
of use for in vivo tumor imaging.
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The Effect of hsa-miR-105 on Prostate Cancer GrowthHoneywell, David R 07 December 2012 (has links)
Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.
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The Effect of hsa-miR-105 on Prostate Cancer GrowthHoneywell, David R 07 December 2012 (has links)
Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.
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The Effect of hsa-miR-105 on Prostate Cancer GrowthHoneywell, David R January 2012 (has links)
Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.
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