p27Kip1deficiency promotes prostate carcinogenesis but does not affect the efficacy of retinoids in suppressing the neoplastic process

Table 5 9cRA inhibits cell proliferation (Ki-67) and induces senescent phenotype in PIN

Genotype	Animals	Cell Type	9cRA	Ki-67%	p	Apo-%	p	Sen-%	p
p27+/+	5	PEC	0	0.8 ± 0.3*		0.4 ± 0.2		0.8 ± 0.4
p27+/+	6	PEC	+	0.6 ± 0.4	ns	0.6 ± 0.2		1.1 ± 0.5
p27+/+	5	PIN	0	1.2		0.3		0.9
p27+/+	5	PIN	+	NA		NA		NA
p27+/-	6	PEC	0	1.4 ± 0.4* **	0.01	0.3 ± 0.2		0.8 ± 0.4
p27+/-	6	PEC	+	1.2 ± 0.5	ns	0.4 ± 0.2	ns	2.7 ± 1.3	0.001
p27+/-	5	PIN	0	2.6 ± 0.4		0.6 ± 0.3		1.0 ± 0.5
p27+/-	6	PIN	+	1.5 ± 0.5	0.001	0.5 ± 0.4	ns	4.8 ± 1.2	0.001
p27-/-	6	PEC	0	1.7 ± 0.5* **		0.3 ± 0.2		1.2 ± 0.4
p27-/-	5	PEC	+	1.6+0.7	ns	0.4 ± 0.2	ns	2.5 ± 1.3	0.001
p27-/-	6	PIN	0	4.6 ± 0.4		0.6 ± 0.3		3.2 ± 0.7
p27-/-	5	PIN	+	3.5 ± 0.5	0.001	0.5 ± 0.4	ns	6.8 ± 2.2	0.001

The above data were obtained from placebo- and 9cRA-treated animals at the time of their sacrifice at 9-12 months of age. PEC, prostate epithelial cells from DLP not associated with PIN; 0, Placebo-treated animals; +, animals treated with 9cRA; PIN (low and high grade) was identified in H&E stained slides. To determine the incidence (%) and frequency of PIN in DLP and AP, 4 μm thick paraffin sections were cut longitudinally through the urethral part of the prostate stepwise at three separate levels 30 μm apart. All resulting slides were labeled consecutively. Proliferating cells were detected by Ki-67 antibody (Ki-67); Cells in apoptosis (Apo-%) were detected by ApopTag kit based on the TUNEL assay; Cells in senescence (Sen-%) were identified by SA-β-Gal staining employing a kit from Cell Signaling. At least 500 PEC or PIN cells were evaluated to determine the percentage of proliferating (Ki-67-%), apoptotic (Apo-%) or cells in senescence (Sen-%); * or ** indicates significant difference (p < 0.05) in the values between corresponding groups.

ISSN: 1471-2407