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Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

Koga F, Kawakami S, Kumagai J, Takizawa T, Ando N, Arai G, Kageyama Y, Kihara K - Br. J. Cancer (2003)

Bottom Line: At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues.Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms.Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

ABSTRACT
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

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Expression of p63 in cultured cells. (A) Agarose gel electrophoresis of RT–PCR products using isoform-specific primer sets. aAs PCR products were undetectable at 30 cycles of PCR amplification, 40 cycles were performed for TAp63. (B) Immunoblotting for p63 protein using the 4A4 antibody.
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fig4: Expression of p63 in cultured cells. (A) Agarose gel electrophoresis of RT–PCR products using isoform-specific primer sets. aAs PCR products were undetectable at 30 cycles of PCR amplification, 40 cycles were performed for TAp63. (B) Immunoblotting for p63 protein using the 4A4 antibody.

Mentions: We also examined p63 expression profiles in cultured normal and neoplastic urothelial cells. ΔNp63 mRNA was abundantly expressed in NHU cells but undetectable in stromal cells (Figure 4AFigure 4


Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

Koga F, Kawakami S, Kumagai J, Takizawa T, Ando N, Arai G, Kageyama Y, Kihara K - Br. J. Cancer (2003)

Expression of p63 in cultured cells. (A) Agarose gel electrophoresis of RT–PCR products using isoform-specific primer sets. aAs PCR products were undetectable at 30 cycles of PCR amplification, 40 cycles were performed for TAp63. (B) Immunoblotting for p63 protein using the 4A4 antibody.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376335&req=5

fig4: Expression of p63 in cultured cells. (A) Agarose gel electrophoresis of RT–PCR products using isoform-specific primer sets. aAs PCR products were undetectable at 30 cycles of PCR amplification, 40 cycles were performed for TAp63. (B) Immunoblotting for p63 protein using the 4A4 antibody.
Mentions: We also examined p63 expression profiles in cultured normal and neoplastic urothelial cells. ΔNp63 mRNA was abundantly expressed in NHU cells but undetectable in stromal cells (Figure 4AFigure 4

Bottom Line: At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues.Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms.Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

ABSTRACT
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

Show MeSH
Related in: MedlinePlus