Growth pattern and citrate production in organ cultures of adult rat ventral prostate

Ma, Keping; Seibel, Werner; Rb, Franklin; Dv, Provenza; Costello, Leslie C.

doi:10.1002/pros.2990030409

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…In support of this, we found reduced mtDNAcn in matched samples from patients before and after SPA that correlated with clinical response, Ki67 levels, and MYC levels. Studies over several decades have indicated that, compared with normal prostate, prostate cancer cells show increased mitochondrial functions that are important for cell proliferation, and our overall results are concordant with these observations (92)(93)(94)(95)(96).…”

Section: Discussionsupporting

confidence: 90%

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

Chen,

Zheng,

Hicks

et al. 2023

JCI Insight

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Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type–specific or tumor cell heterogeneity in mtDNAcn. These studies have often produced unclear results, particularly in prostate cancer. Herein, we developed a multiplex in situ method to spatially quantify cell type–specific mtDNAcn. We show that mtDNAcn is increased in luminal cells of high-grade prostatic intraepithelial neoplasia (HGPIN), is increased in prostatic adenocarcinomas (PCa), and is further elevated in metastatic castration-resistant prostate cancer. Increased PCa mtDNAcn was validated by 2 orthogonal methods and is accompanied by increases in mtRNAs and enzymatic activity. Mechanistically, MYC inhibition in prostate cancer cells decreases mtDNA replication and expression of several mtDNA replication genes, and MYC activation in the mouse prostate leads to increased mtDNA levels in the neoplastic prostate cells. Our in situ approach also revealed elevated mtDNAcn in precancerous lesions of the pancreas and colon/rectum, demonstrating generalization across cancer types using clinical tissue samples.

show abstract

Section: Discussionsupporting

confidence: 90%

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

Chen,

Zheng,

Hicks

et al. 2023

JCI Insight

View full text Add to dashboard Cite

show abstract

“…In support of this, we found reduced mtDNAcn in matched samples from patients before and after SPA that correlated with clinical response, Ki67 levels and MYC levels. Studies over several decades have indicated that, compared with normal prostate, prostate cancer cells show increased mitochondrial functions that are important for cell proliferation, and our overall results are concordant with these observations (94)(95)(96)(97)(98).…”

Section: Why Is Mtdnacn Increased?supporting

confidence: 90%

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

Chen

Zheng

Hicks

et al. 2023

Preprint

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Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn. These studies have often produced unclear results, particularly in prostate cancer. Herein, we developed a multiplexin situmethod to spatially quantify cell type specific mtDNAcn. We show that mtDNAcn is increased in luminal cells of high-grade prostatic intraepithelial neoplasia (HGPIN), is increased in prostatic adenocarcinomas (PCa), and is further elevated in metastatic castration-resistant prostate cancer. Increased PCa mtDNAcn was validated by two orthogonal methods and is accompanied by increases in mtRNAs and enzymatic activity. Mechanistically, MYC inhibition in prostate cancer cells decreases mtDNA replication and expression of several mtDNA replication genes, and MYC activation in the mouse prostate leads to increased mtDNA levels in the neoplastic prostate cells. Ourin situapproach also revealed elevated mtDNAcn in precancerous lesions of the pancreas and colon/rectum, demonstrating generalization across cancer types using clinical tissue samples.

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“…Histological examination of the compact region demonstrated the dominance of acinar structures lined with columnar epithelium (secretory cells) with occasional basal cells. Thus far our studies with pig prostate have demonstrated that it provides an extremely valuable model for citrate relationships [49,52], especially when used in conjunction with rat prostate studies. One might also consider the use of pig seminal vesicles as a model for citrate relationships.…”

Section: Citrate Relationships In Normal and Neoplastic Human Prostatementioning

confidence: 99%

Concepts of citrate production and secretion by prostate 1. Metabolic relationships

1991

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Accumulation and secretion of extraordinarily high levels of citrate are principal functions of the prostate gland of humans and other animals. To achieve this, prostate secretory cells must possess unique metabolic relationships which distinguish them from virtually all other cells. Furthermore, citrate metabolism is markedly altered in benign prostatic hyperplasia (BPH) and in prostatic carcinoma (CA). This review assimilates existing information and presents current concepts related to 1) the pathway of metabolism associated with net citrate production, 2) the involvement of transporting mechanisms associated with citrate secretion, 3) energy implications of citrate production, 4) altered metabolic relationships in BPH and CA, and 5) the importance of citrate relationships as biochemical markers for characterizing prostate secretory epithelial cells. It is hoped that this review will bring attention to the importance and urgency of elucidating and understanding the metabolic relationships associated with citrate production by normal and neoplastic prostate epithelial cells. Research in these areas has been severely neglected despite the fact that the combined incidence of BPH and CA constitutes the most prevalent neoplastic disease among men.

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Growth pattern and citrate production in organ cultures of adult rat ventral prostate

Cited by 10 publications

References 14 publications

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

Concepts of citrate production and secretion by prostate 1. Metabolic relationships

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