Copy number aberrations of the <i>CYP2A6</i> and neighboring genes in human bladder cancer.

<p>(A) Copy numbers of <i>CYP2A6</i>, <i>CYP2A7</i>, <i>CYP2B6</i>, <i>CYP2A13</i>, <i>CYP2F1</i>, and <i>TGFB1</i> on human chromosomal region 19q13.2 in eight bladder cancer cell lines. (B) <i>CYP2A6</i> amplification in primary bladder tumors. <i>CYP2A6</i> copy number aberrations in each case of superficial (n = 9) and invasive (n = 9) bladder cancers are shown.</p

BBN-induced bladder carcinogenesis in rodents.

<p>(A) Experimental schedule of bladder cancer induction by BBN in rats (scheme); the time of superficial bladder cancer appearance is indicated. Representative images of hematoxylin/eosin-stained normal urothelium, and papillary carcinoma (week 40) are shown; the inset images show higher magnification. (B) Experimental schedule of bladder cancer induction by BBN in mice (scheme); chronological appearance of hyperplasia, dysplasia, carcinoma <i>in situ</i> (CIS), and invasive bladder cancer is indicated. Representative images of hematoxylin/eosin-stained normal urothelium, hyperplasia (week 8), dysplasia (week 12), severe dysplasia (week 20), CIS (week 20), and invasive carcinoma (week 26) are shown; the inset images show higher magnification.</p

Array CGH analysis of invasive bladder tumors in BBN-treated mice.

<p>(A) Whole-genome array CGH profile. (B) Detailed array CGH profile of mouse chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D. Tumor to normal copy number ratios for microarray probes expressed as log₂ values are shown by dots. Red dots indicate significant copy number gain (log₂ ratio > +1).</p

Immunohistochemical analysis of CYP2A6 protein expression in human bladder cancer.

<p>(A) CYP2A6 immunoreactivity in a representative primary bladder tumor containing superficial and invasive lesions. (B and C) CYP2A6 distribution in indicated types of lesions. Images are obtained at low (B) and high (C) magnification. (D) Quantification of CYP2A6 immunoreactivity in primary bladder cancers. Primary bladder tumors (n = 104) were classified into those with superficial papillary lesions (n = 53), invasive aggregated lesions (n = 108), and invasive scattered lesions (n = 132). *p < 0.01 (invasive aggregated versus superficial papillary lesions and invasive scattered versus invasive aggregated lesions; Student’s <i>t</i>-test).</p

Validation of the array CGH results by qPCR.

<p>Copy number changes of representative genes, including the amplicons on mouse chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D, are shown.</p