Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0282612 (
PIN
)
2,291
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Laminin 5 is an extracellular matrix protein integral to the formation of the hemidesmosomes that attach normal basal cells to the underlying basal lamina. We have shown that these hemidesmosomal complexes are lost in prostate carcinoma, possibly allowing malignant cells to detach from the anchoring structures and then to invade and migrate through the adjacent tissue. Our previous immunohistochemical studies of normal and malignant human prostate tissue demonstrated that the laminin subchains alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 were all expressed as normal components of the basal lamina surrounding prostate glands. Although most of these subchains were also expressed by the de novo basal lamina synthesized by prostate carcinoma, the gamma 2 subchain of
laminin 5
was not detected. In an effort to investigate the role
laminin 5
plays in the tumorigenesis of prostate carcinoma, the protein expression of the three subchains of
laminin 5
(alpha 3, beta 3, and gamma 2) was compared in normal prostate,
prostatic intraepithelial neoplasia
, and invasive carcinoma using immunohistochemistry. The results showed that the protein for the alpha 3 subchain of
laminin 5
is retained by both normal prostate epithelium and prostate carcinoma, but the beta 3 and the gamma 2 subchains were not detected in invasive carcinoma. Despite the absence of the gamma 2 protein, however, the carcinoma cells continued to express substantial amounts of the gamma 2 mRNA. Although it is unclear how the gene for the gamma 2 subchain of
laminin 5
is regulated, results of this study suggest that there is a post-transcriptional defect in the expression of the gamma 2 subchain that occurs during the progression from a premalignant lesion to invasive carcinoma. As
laminin 5
is a component of the anchoring filaments, the failure to express the gamma 2 subchain may contribute to the failure to form anchoring filaments and hemidesmosomes. This failure of hemidesmosome formation results in a less stable epithelial-stromal junction, which may allow malignant cells more potential to invade and spread through adjacent structures.
...
PMID:Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant and normal prostate. 886 81
The progressive loss of
laminin 5
and the alpha6beta4 integrin is a characteristic of the transition of
prostatic intraepithelial neoplasia
(
PIN
) to invasive human prostate cancer. Our objective was to determine if the loss of the interaction with
laminin 5
would influence the ability of human epithelial cells to respond to DNA damage. Three cellular damage responses to ionizing radiation (IR) were analyzed including G2 progression, cdc2 phosphorylation, and cell survival. The adhesion of normal human prostate epithelial cells to
laminin 5
amplified the G2 arrest induced by IR, and depends on a known cell binding domain of
laminin 5
. The alteration of G2 arrest was confirmed by an inhibition of phospho-cdc2 nuclear translocation. In contrast, a prostate epithelial cancer cell line blocked in G2 independent of adhesion to
laminin 5
. The survival of these cell lines in response to IR was unaffected by adhesion to
laminin 5
. These results suggest that cell adhesion to
laminin 5
in normal cells will amplify the IR induced G2 cell cycle progression block without altering cell survival. The loss of
laminin 5
and the alpha6beta4 integrin in
PIN
lesions may contribute to the selection and progression of genetically unstable cell types via attenuation of a DNA damage induced G2 arrest.
...
PMID:Integrin-dependent amplification of the G2 arrest induced by ionizing radiation. 1611 62
