Abstract

This review analyzes the potential impact of milk-induced signal transduction on the pathogenesis of prostate cancer (PCa). Articles in PubMed until November 2021 reporting on milk intake and PCa were reviewed. Epidemiological studies identified commercial cow milk consumption as a potential risk factor of PCa. The potential impact of cow milk consumption on the pathogenesis of PCa may already begin during fetal and pubertal prostate growth, critical windows with increased vulnerability. Milk is a promotor of growth and anabolism via activating insulin-like growth factor-1 (IGF-1)/phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin complex 1 (mTORC1) signaling. Estrogens, major steroid hormone components of commercial milk of persistently pregnant dairy cows, activate IGF-1 and mTORC1. Milk-derived signaling synergizes with common driver mutations of the PI3K/AKT/mTORC1 signaling pathway that intersect with androgen receptor, MFG-E8, MAPK, RUNX2, MDM4, TP53, and WNT signaling, respectively. Potential exogenously induced drivers of PCa are milk-induced elevations of growth hormone, IGF-1, MFG-E8, estrogens, phytanic acid, and aflatoxins, as well as milk exosome-derived oncogenic microRNAs including miR-148a, miR-21, and miR-29b. Commercial cow milk intake, especially the consumption of pasteurized milk, which represents the closest replica of native milk, activates PI3K-AKT-mTORC1 signaling via cow milk’s endocrine and epigenetic modes of action. Vulnerable periods for adverse nutrigenomic impacts on prostate health appear to be the fetal and pubertal growth periods, potentially priming the initiation of PCa. Cow milk-mediated overactivation of PI3K-AKT-mTORC1 signaling synergizes with the most common genetic deviations in PCa, promoting PCa initiation, progression, and early recurrence.

Highlights

  • Prostate cancer (PCa) is the sixth leading cause of cancer death among men worldwide and is expected to reach 2.3 million new cases and 740,000 deaths by 2040[1]

  • Milk miR-125b- and miR-30d-mediated suppression of p53 attenuates the activity of crucial negative regulators of androgen and mechanistic target of rapamycin complex 1 (mTORC1) signaling, both related to PCa pathogenesis [Figure 2B][494,498]

  • As shown in this review, milk consumption provides a symphony of signals activating phosphatidylinositol-3 kinase (PI3K)-AKT-mTORC1 and synergistically operates on overactivated PI3K-AKT-mTORC1 signaling pathways of PCa[21,154]

Read more

Summary

Introduction

Prostate cancer (PCa) is the sixth leading cause of cancer death among men worldwide and is expected to reach 2.3 million new cases and 740,000 deaths by 2040[1]. DNMT1 is a major target of miR-148a[109,110], which explains MEX-mediated suppression of DNMT1 expression[418,438], a pivotal postnatal mechanism modifying epigenetic regulation activating mTORC1 signaling[153,439,443,474].

Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.