The immunohistochemical localization of drug‐metabolizing enzymes in prostate cancer

Murray, Graeme I.; Taylor, Valerie; McKay, Judith; Weaver, Richard J.; Ewen, S. W. B.; Melvin, William T.; Burke, Mary

doi:10.1002/path.1711770208

Cited by 68 publications

(58 citation statements)

References 30 publications

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“…Gentamicin, 3-cyclohexylamino-1-propanesulfonic acid (CAPS), Kodak XOMAT films, antibody raised against actin, diaminobenzidine (DAB), sodium bicarbonate, HEPES, DNase I, 3-N-morpholinopropane-sulfonic acid (MOPS), SDS, random primers, and BSA were purchased from Sigma. Rabbit polyclonal anti-human Glutathione-S-transferase (GST)a antibody (Mehta et al 1994, Murray et al 1995 Methods Animals: in utero exposure to anti-androgens Fifteen pregnant rats (Sprague-Dawley rats from Charles River Laboratories, St Aubin les Elbeuf, France) per group were administered vehicle (methylcellulose) or flutamide by daily gavage from day 10 of gestation (GD 10) up to the day before delivery (GD 21 or 22). This period includes the period of male internal and external sex differentiation.…”

Section: Methodsmentioning

confidence: 99%

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

Benbrahim‐Tallaa¹,

Siddeek²,

Bözec³

et al. 2007

Journal of Endocrinology

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Fetal androgen disruption, induced by the administration of anti-androgen flutamide (0 . 4, 2, and 10 mg/kg day) causes a long-term apoptosis in testicular germ cells in adult male rat offspring. One of the questions raised by this observation is the role of the Sertoli cells in the adult germ cell apoptotic process. It is shown here that Sertoli cells originating from 15-day-old rats treated in utero with the anti-androgen (10 mg/kg d) did no longer protect adult germ cells against apoptosis. Indeed, untreated spermatocytes or spermatids exhibited increased (P!0 . 0001) active caspase-3 levels when co-cultured with Sertoli cells isolated from rat testes exposed in utero to the anti-androgen. This alteration of Sertoli cell functions was not due to modifications in the androgen signal in the adult (90-day-old) animals, since plasma testosterone and estradiol, androgen receptor expression, and androgentargeted cell number (e.g., Sertoli cells in the seminiferous tubules) were not affected by the fetal androgen disruption. In contrast, this inability of Sertoli cells to protect germ cells against apoptosis could be accounted for by the potential failure of Sertoli cell functions. Indeed, adult testes exposed in utero to anti-androgens displayed decreased levels of several genes mainly expressed in adult Sertoli cells (anti-Mullerian hormone receptor type II (AMHR2), Cox-1, cyclin D2, cathepsin L, and GSTa). In conclusion, fetal androgen disruption may induce alterations of Sertoli cell activity probably related to Sertoli cell maturation, which potentially leads to increased adult germ cell apoptosis.

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Section: Methodsmentioning

confidence: 99%

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

Benbrahim‐Tallaa¹,

Siddeek²,

Bözec³

et al. 2007

Journal of Endocrinology

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“…CYP3A43 mRNA has been detected mainly in the prostate, testis, and liver, but at relatively low levels (Domanski et al 2001, Westlind et al 2001. With respect to the CYP3A prostate expression, Murray et al (1995b) found no CYP3A protein in normal prostate tissue, but they detected expression in 61% of tumor samples. In contrast, Moilanen et al (2007), focusing specifically on CYP3A5, detected CYP3A5 protein in normal and tumoral prostate tissue, but the defective CYP3A5*3 allele seemed to have no effect on protein expression.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer

Leskelä

Honrado²,

Montero‐Conde

et al. 2007

Endocr Relat Cancer

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Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.

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“…The expression of CYP3A5 was reported in prostate and other extrahepatic tissues by a number of researchers using the RT-PCR methodology (Murray et al, 1995;Yamakoshi et al, 1999;Finnstrom et al, 2001;Nishimura et al, 2003). A more recent study reported the CYP3A5 expression in normal prostate cells but not in prostate cancer cells (Leskelä et al, 2007).…”

Section: Resultsmentioning

confidence: 98%

Detection of Cytochrome P450-2A6, -3A5 and -4B1 with Real-Time Polymerase Chain Reaction in Prostate Tissue

Zencir

Alptekin

Çeliktaş

et al. 2008

Zeitschrift Für Naturforschung C

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Cytochrome P450 (CYP) is a heme-containing enzyme superfamily metabolizing a wide variety of xenobiotics, including drugs and carcinogens. The majority of CYP genes are expressed in the liver, however, some CYP isoforms are also reported for a number of extra hepatic tissues. We analyzed Cytochrome P450Ð2A6, -3A5 and -4B1 mRNAs using realtime reverse-transcriptase polymerase chain reaction (RT-PCR) in a total of 21 homogenized prostate tissues with or without malignancy. We detected a consistent expression of CYP2A6 and CYP3A5 in all, and of CYP4B1 in some (11/21) of the samples at mRNA level. Neither the histopathological status nor the smoking habit of the individuals affected CYP4B1 expression. Our results reflect possible roles for these particular CYPs in therapy and protection of prostate tissue.

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The immunohistochemical localization of drug‐metabolizing enzymes in prostate cancer

Cited by 68 publications

References 30 publications

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer

Detection of Cytochrome P450-2A6, -3A5 and -4B1 with Real-Time Polymerase Chain Reaction in Prostate Tissue

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