MYC Overexpression Induces Prostatic Intraepithelial Neoplasia and Loss of Nkx3.1 in Mouse Luminal Epithelial Cells

Objectives- Prostate is a bromusculoglandular structure situated at the neck of urinary bladder. It enlarges due to benign hyperplasia of prostate (BHP), prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. Enlargement of prostate is associated with raised serum level of prostate-specic antigen (PSA) and altered expression of estrogen receptor (ER) and progesterone receptor (PR). The aim of our study is to correlate the histopathology, PSA levels and altered expression of ER and PR by immunohistochemistry in different prostatic growth lesions. Methodology- Patients diagnosed as having prostatic growth were enrolled and their serum PSA levels were noted. Histopathological examination and immunohistochemical analysis of prostatic tissues for ER and PR were carried out to nd out correlation of different type of growth with serum PSA level and expression of ER and PR. Results- A total 96 cases studied of them 61(63.54%) patients presented with BHP, 20(20.83%) patients with BHP with chronic prostatitis, 3 patients presented with metaplastic changes, 5 cases with of PIN and 6 patients presented with adenocarcinoma with different Gleason score. PR expression positivity in epithelial cells and stromal cells of BHP cases were 51(83.6%) and 53(86.88%) respectively. Patients presented with adenocarcinoma showed only 33.33 %( 2cases) positivity in epithelial cells and 50% (3cases) positivity in stromal cells. Serum PSA level were signicantly higher in adenocarcinoma patients as compare to BHP patients. Conclusion- By observing these ndings it can be suggested that and antiprogesterone therapy may be helpful in the treatment of prostatic adenocarcinoma.

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523: Risk of Prostate Cancer on Re-Biopsy Following a Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) is Related to the Number of Cores Sampled

The Journal of Urology ◽

10.1016/s0022-5347(18)34763-3 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 142-143 ◽

Cited By ~ 1

Author(s):

Mehsati Herawi ◽

Christina Cavallo ◽

Hillel Kahane ◽

Jonathan I. Epstein

Keyword(s):

Prostate Cancer ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

High Grade

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1714: Comparison of Contrast Enhanced Color Doppler Targeted Versus Extended 10 Core Repeat Biopsy Strategy in Patients with Previous Prostatic Intraepithelial Neoplasia (HGPIN)

The Journal of Urology ◽

10.1016/s0022-5347(18)35836-1 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 465-465

Author(s):

Christian Wiunig ◽

Josef Pointner ◽

Stefan Obwexer ◽

Ralph Meyer-Venter ◽

Michael Aigner ◽

...

Keyword(s):

Color Doppler ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

Repeat Biopsy ◽

Contrast Enhanced

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Glyoxalase 1 Expression as a Novel Diagnostic Marker of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Cancer

Cancers ◽

10.3390/cancers13143608 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3608

Author(s):

Liliana Rounds ◽

Ray B. Nagle ◽

Andrea Muranyi ◽

Jana Jandova ◽

Scott Gill ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Marker ◽

Precancerous Lesion ◽

Immunohistochemical Analysis ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

Glycolytic Flux ◽

Gleason Grade ◽

High Grade ◽

Glyoxalase 1

Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.

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Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells

Nature Communications ◽

10.1038/s41467-021-23957-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Patrick D. Rädler ◽

Barbara L. Wehde ◽

Aleata A. Triplett ◽

Hridaya Shrestha ◽

Jonathan H. Shepherd ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Epithelial Cells ◽

Triple Negative ◽

Molecular Subtype ◽

Ras Signaling ◽

Preneoplastic Lesions ◽

Independent Manner ◽

Oncogenic Ras ◽

Luminal Epithelial Cells

AbstractClaudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells.

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The In Vitro Effect of Steroid Hormones, Arachidonic Acid, and Kinases Inhibitors on Aquaporin 1, 2, 5, and 7 Gene Expression in the Porcine Uterine Luminal Epithelial Cells during the Estrous Cycle

Cells ◽

10.3390/cells10040832 ◽

2021 ◽

Vol 10 (4) ◽

pp. 832

Author(s):

Damian Tanski ◽

Agnieszka Skowronska ◽

Malgorzata Tanska ◽

Ewa Lepiarczyk ◽

Mariusz T. Skowronski

Keyword(s):

Arachidonic Acid ◽

Epithelial Cells ◽

Steroid Hormones ◽

Estrous Cycle ◽

Kinase Inhibitor ◽

Mapk Signaling ◽

Mapk Kinase ◽

Vitro Effect ◽

Luminal Epithelial Cells

Aquaporins (AQPs) are integral membrane proteins, which play an important role in water homeostasis in the uterus. According to the literature, the expression of aquaporins in reproductive structures depends on the local hormonal milieu. The current study investigated the effect of selected PKA kinase inhibitor H89 and MAPK kinase inhibitor PD98059, on the expression of AQP1, 2, 5, and 7, and steroid hormones (E2), progesterone (P4), and arachidonic acid (AA) in the porcine endometrium on days 18–20 and 2–4 of the estrous cycle (the follicular phase where estrogen and follicle-stimulating hormone (FSH) are secreted increasingly in preparation for estrus and the luteal phase where the ovarian follicles begin the process of luteinization with the formation of the corpus luteum and progesterone secretion, respectively). The luminal epithelial cells were incubated in vitro in the presence of the aforementioned factors. The expression of mRNA was determined by the quantitative real-time PCR technique. In general, in Experiment 1, steroid hormones significantly increased expression of AQP1, 2, and 5 while arachidonic acid increased expression of AQP2 and AQP7. On the other hand, MAPK kinase inhibitor significantly decreased the expression of AQP1 and 5. In Experiment 2, E2, P4, or AA combined with kinase inhibitors differentially affected on AQPs expression. E2 in combination with PKA inhibitor significantly decreased expression of AQP1 but E2 or P4 combined with this inhibitor increased the expression of AQP5 and 7. On the contrary, E2 with PD98059 significantly increased AQP5 and AQP7 expression. Progesterone in combination with MAPK kinase inhibitor significantly downregulated the expression of AQP5 and upregulated AQP7. Arachidonic acid mixed with H89 or PD98059 caused a decrease in the expression of AQP5 and an increase of AQP7. The obtained results indicate that estradiol, progesterone, and arachidonic acid through PKA and MAPK signaling pathways regulate the expression of AQP1 and AQP5 in the porcine luminal epithelial cells in the periovulatory period.

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