Age-Associated Changes in Histology and Gene-Expression Profile in the Rat Ventral Prostate

Lau, Kin‐Mang; Tam, Neville N.C.; Thompson, Christopher J.; Cheng, Robert; Leung, Yuet-Kin; Ho, Shuk‐Mei

doi:10.1097/01.lab.0000069519.06988.24

Cited by 37 publications

(42 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ventral prostate normally atrophies with aging, and decreasing testosterone levels with age correlate with decreased weight of the ventral prostate (Isaacs 1984, Bosland 1992, Lau et al 2003. Interestingly, in the current studies a shift from the general age-related atrophy toward hyperplasia of the ventral prostate was observed following exposure to the contaminant mixture and to anti-androgens in particular.…”

Section: Reproductive Aging In Malesmentioning

confidence: 50%

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

et al. 2014

View full text Add to dashboard Cite

This study examined late-life effects of perinatal exposure of rats to a mixture of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, u.v.-filters, bisphenol A, parabens, and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.

show abstract

Section: Reproductive Aging In Malesmentioning

confidence: 50%

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The sets of genes whose expression was threefold altered following hormonal treatment in HOSE cell lines or in OVCA cell lines in a consistent manner were identified by t-statistics analyses as described earlier Lau et al, 2003). A total of 171 genes were differentially expressed in all three immortalized HOSE cell lines after P4 treatment, and 135 genes were identified as having changed expression in all three OVCA cell lines after P4 exposure (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…A cDNA microarray containing 2388 known transcripts, together with the Tyramide Amplification Systemt and t statistics Lau et al, 2003), were employed to identify genes whose expression are altered after exposure of nontumorigenic human OSE (HOSE) cell lines or OCa (OVCA) cell lines to 10 À 6 M of P4. We then selected those whose expression are (1) lost or significantly reduced in OVCA cell lines when compared to HOSE cell lines and (2) are upregulated by P4 only in the malignant cell lines and not in the nontumorigenic cell lines.…”

Section: Introductionmentioning

confidence: 99%

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling

et al. 2005

Self Cite

View full text Add to dashboard Cite

“…Briefly, the fluorescent intensity of each spot was calculated by local median background subtraction. Dye bias and experimental and systematic variations were removed as described before (Yang et al, 2002;Lau et al, 2003). Log ratios were centered on zero to achieve within-slide normalization and across-slide comparisons.…”

Section: Rna Isolation Probe Preparation and Transcriptome Comparisonmentioning

confidence: 99%

Profiling estrogen-regulated gene expression changes in normal and malignant human ovarian surface epithelial cells

et al. 2005

Self Cite

View full text Add to dashboard Cite

Estrogens regulate normal ovarian surface epithelium (OSE) cell functions but also affect epithelial ovarian cancer (OCa) development. Little is known about how estrogens play such opposing roles. Transcriptional profiling using a cDNA microarray containing 2400 named genes identified 155 genes whose expression was altered by estradiol-17b (E2) in three immortalized normal human ovarian surface epithelial (HOSE) cell lines and 315 genes whose expression was affected by the hormone in three established OCa (OVCA) cell lines. All but 19 of the genes in these two sets were different. Among the 19 overlapping genes, five were found to show discordant responses between HOSE and OVCA cell lines. The five genes are those that encode clone 5.1 RNAbinding protein (RNPS1), erythrocyte adducin a subunit (ADD1), plexin A3 (PLXNA3 or the SEX gene), nuclear protein SkiP (SKIIP), and Rap-2 (rap-2). RNPS1, ADD1, rap-2, and SKIIP were upregulated by E2 in HOSE cells but downregulated by estrogen in OVCA cells, whereas PLXNA3 showed the reverse pattern of regulation. The estrogen effects was observed within 6-18 h of treatment. In silicon analyses revealed presence of estrogen response elements in the proximal promoters of all five genes. RNPS1, ADD1, and PLXNA3 were underexpressed in OVCA cell lines compared to HOSE cell lines, while the opposite was true for rap-2 and SKIIP. Functional studies showed that RNPS1 and ADD1 exerted multiple antitumor actions in OVCA cells, while PLXNA3 only inhibited cell invasiveness. In contrast, rap-2 was found to cause significant oncogenic effects in OVCA cells, while SKIIP promotes only anchorageindependent growth. In sum, gene profiling data reveal that (1) E2 exerts different actions on HOSE cells than on OVCA cells by affecting two distinct transcriptomes with few overlapping genes and (2) among the overlapping genes, a set of putative oncogenes/tumor suppressors have been identified due to their differential responses to E2 between the two cell types. These findings may explain the paradoxical roles of estrogens in regulating normal and malignant OSE cell functions.

show abstract

Age-Associated Changes in Histology and Gene-Expression Profile in the Rat Ventral Prostate

Cited by 37 publications

References 94 publications

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling

Profiling estrogen-regulated gene expression changes in normal and malignant human ovarian surface epithelial cells

Contact Info

Product

Resources

About