Disease relevance of CDH3

• Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin [1].
• P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation [2].
• Based on information derived from a previous genome-wide cDNA microarray analysis of microdissected pancreatic ductal adenocarcinoma (PDAC), we focused on P-cadherin as one of the genes most strongly overexpressed in the great majority of PDACs [3].
• Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases [3].
• The expression of P-cadherin in human prostate cancer development has not been investigated previously [4].
• CDH3 was overexpressed in the majority of pancreatic cancer and various other malignancies, including gastric and colorectal cancers, but not in their noncancerous counterparts or in many normal adult tissues [5].

Psychiatry related information on CDH3

• Chronic delusional psychosis with hallucinations (CDHP) is commonly assumed to complicate the later stages of Parkinson's disease, as a side effect of antiparkinsonian medication [6].

High impact information on CDH3

• These results establish the molecular etiology of HJMD and implicate for the first time a cadherin molecule in the pathogenesis of a human hair and retinal disorder [1].
• 1. This region contains CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles [1].
• In addition, transfection of a normal-appearing squamous epithelial cell line with N-cadherin resulted in downregulation of both E- and P-cadherin and a scattered fibroblastic phenotype [7].
• We showed that a squamous cell carcinoma-derived cell line expressed N-cadherin and displayed a scattered fibroblastic phenotype along with decreased expression of E- and P-cadherin [7].
• In spite of the deformed appearance of the superficial cells in the presence of anti-E-cadherin IgG, these cells express the differentiation marker filaggrin, do not express P-cadherin, and concentrate desmoplakin at their cell-cell borders, consistent with the pattern in normally stratified cultures and in epidermis [8].

Chemical compound and disease context of CDH3

• P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type [9].
• These results demonstrate that the expression of the basal cell marker P-cadherin is lost in prostate cancer development and that in vivo mechanisms other than cytosine methylation regulate this consistent loss of expression [4].
• In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative) [10].
• Double-label immunofluorescence has been used to stain a panel of 22 oral squamous cell carcinomas with antibodies to ten proteins, including E- and P-cadherin, the major keratinocyte integrin subunits, and alpha-, beta- and gamma-catenin [11].
• We have compared expression of involucrin, E-cadherin and P-cadherin in cultures of normal keratinocytes and in five different lines derived from squamous cell carcinomas (SCCs), using Northern analysis and immunofluorescence [12].

Biological context of CDH3

• The normal P-cadherin-negative breast epithelial cells showed consistent CDH3 promoter methylation [2].
• This is the first pathogenic missense mutation reported in CDH3 and the second mutation found to underlie hypotrichosis with juvenile macular dystrophy [13].
• Recently, we identified a frameshift mutation in the CDH3 gene encoding P-cadherin as the proximal cause of hypotrichosis with juvenile macular dystrophy in four families [13].
• The human homologue CDH3 was mapped to chromosome 16q24.1-qter by analyzing human/mouse somatic cell hybrids [14].
• On the basis of the nucleotide sequences of the resultant PCR products, multiple cadherin subtypes (E-, N-, P-cadherin, and cadherin-4, -6, and -11) were found to be present in these normal and malignant tissues and cells [15].

Anatomical context of CDH3

• Cytosine methylation of this region occurs in P-cadherin-negative prostate cancer cell lines but not in cell lines expressing this gene [4].
• P-cadherin was determined to be the predominant cadherin subtype in normal peritoneum, peritoneal effusions and Stage II tumor masses [15].
• Together, our studies show no apparent effect on adult mammary gland or tumor behavior by inappropriate expression of P-cadherin in normal mammary epithelial cells [16].
• P-cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS [17].
• Thus, aberrant expression of P-cadherin may be a useful marker of invasive or aggressive clinical behavior in glandular lesions of the cervix [18].

Associations of CDH3 with chemical compounds

• P-cadherin was detected in most, but not all, luminal epithelial cells, and was appropriately localized to cell-cell borders [16].
• It has been demonstrated here that during cisplatin-induced apoptosis of human embryo retinoblasts both E- and P-cadherin were degraded by caspases, giving initially major polypeptide products of apparent molecular weights 48 K and 104 K respectively [19].
• Like E- and P-cadherin, Ca(2+) treatment of normal and tumor-derived human keratinocytes resulted in c-Yes (and c-Src and Fyn), as well as their putative substrate p120(CTN), being recruited to cell-cell contacts [20].
• We studied the developmental expression of nephrin, ZO-1 and P-cadherin in normal fetal kidneys and in NPHS1 kidneys [21].
• Adhesion of cultured melanocytes to keratinocyte monolayers is abolished by pre-treatment of the melanocytes with trypsin/EDTA, which degrades E- and P-cadherins, is greatly reduced by anti-E-cadherin antibodies and is slightly reduced by antibodies to P-cadherin, alpha 2, alpha 3 and beta 1 integrins [22].

Physical interactions of CDH3

• Collectively, these findings suggest that the regulated expression of P-cadherin/beta-catenin complexes in ovarian tumor cells may represent a key step in disease progression [15].

Regulatory relationships of CDH3

• In contrast to normal melanocytes, eight of nine melanoma cell lines lacked E-cadherin (or expressed markedly reduced levels) and five were negative for P-cadherin [22].
• The results suggest that HGF/SF may regulate cell adhesion in gastric carcinomas via E- and P-cadherin expression at the protein level [23].
• In the MCF-7/AZ breast cancer cell line, blocking estrogen receptor-alpha signaling with the antiestrogen ICI 182,780 induced an increase of P-cadherin, which coincided with induction of in vitro invasion [24].

Other interactions of CDH3

• Overexpression of P-cadherin was strongly associated with cytoplasmic accumulation of one of the catenins, p120ctn, and cadherin switching in PDAC cells [3].
• Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin [25].
• Our data establish recessive mutations in CDH3 as the molecular cause of hypotrichosis with juvenile macular dystrophy and expand our understanding of the pathophysiology of this intriguing disorder [13].
• (ii) To ascertain whether expression of P-cadherin is independent of or correlated with expression of its associated proteins--E-cadherin, beta-catenin, and gamma-catenin [26].
• P-cadherin present in adenomas was functional with regard to catenin binding, and its expression was independent of APC mutational status [26].

Analytical, diagnostic and therapeutic context of CDH3

• By immunohistochemistry, we show that P-cadherin expression is restricted to the cell-cell border of basal epithelial cells in 30 normal prostate samples [4].
• An increase in P-cadherin mRNA and protein expression levels in ovarian tumor masses with progression to later stages of the disease state was confirmed by Northern and Western blot analysis, respectively [15].
• Immunoprecipitation studies demonstrated that P-cadherin was capable of interacting with beta-catenin in these normal and malignant tissues and cells [15].
• In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies [27].
• Both immunofluorescence and immunoblot studies suggested that P-cadherin may be involved in pioneer contact adhesion of TW-039 cells [28].

References