Prohibitin mutations are uncommon in prostate cancer families linked to chromosome 17q

White, Kirsten A.; Lange, Ethan M.; Ray, Anna M.; Wojno, Kirk J.; Cooney, Kathleen A.

doi:10.1038/sj.pcan.4500878

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Given the location and presumed function of this gene in prostate cancer, we felt it represented a plausible candidate gene for the prostate cancer susceptibility gene on 17q. However, sequence analysis of DNA from one family member from each of 32 multiplex prostate cancer families from the UM-PCGP with evidence of prostate cancer linkage to 17q failed to uncover obvious deleterious PHB mutations (White et al 2006). The breast cancer susceptibility gene BRCA1 is located at approximately 71 cM based on the deCODE map and thus is within the 2-LOD but not the 1-LOD support interval.…”

Section: Discussionmentioning

confidence: 99%

Fine-mapping the putative chromosome 17q21–22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis

Lange¹,

Robbins

Gillanders

et al. 2006

Hum Genet

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Prostate cancer linkage studies have suggested the existence of a prostate cancer susceptibility gene on chromosome 17q21-22. We now report the results of an extended linkage analysis including 95 new multiplex prostate cancer families and 9 additional microsatellite markers resulting in a maximum LOD score of 2.99 at approximately 81-82 cM for all 453 pedigrees. Results from these 95 new pedigrees provide additional support for a chromosome 17q21-22 prostate cancer susceptibility gene. Inclusion of the 9 additional markers significantly reduced the size of the candidate region, as defined using a 1-LOD support interval, especially when focusing analyses on subsets of pedigrees with four or more confirmed affecteds or average age of diagnosis less than or equal to 65 years. A novel subset analysis of only those families (n = 147) that had four or more prostate cancer cases and an average age of prostate cancer diagnosis < or = 65 years results in a maximum LOD score of 5.49 at 78 cM with a 1-LOD support interval of 10 cM. This large set of pedigrees with four more prostate cancer cases characterized by early-onset disease will serve as a useful resource for identifying the putative 17q21-22 prostate cancer susceptibility gene.

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Section: Discussionmentioning

confidence: 99%

Fine-mapping the putative chromosome 17q21–22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis

Lange¹,

Robbins

Gillanders

et al. 2006

Hum Genet

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“…It inhibits DNA synthesis and cell growth by regulating E2F1 function (Wang et al 1999a(Wang et al , 1999b. Human prohibitin has been mapped to chromosome 17q21 and is ubiquitously expressed (Sato et al 1992;White et al 2006). It is an evolutionarily conserved protein localized in the mitochondria (Nijtmans et al 2002) and nucleus (Fusaro et al 2003;Gamble et al 2004), but its exact function is still controversial (Chowdhury et al 2007).…”

Section: Discussionmentioning

confidence: 96%

Comparative proteomic analysis reveals differentially expressed proteins regulated by a potential tumor promoter, BRE, in human esophageal carcinoma cells

Chen

Pan

Tang

et al. 2008

Biochem. Cell Biol.

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Esophageal tumorigenesis is a complex and cascading process, involving the interaction of many genes and proteins. In this study, we have used the comparative proteomic approach to identify tumor-associated proteins and explore the carcinogenic mechanisms. Two-dimensional electrophoresis (2-DE) and MALDI-TOF MS analysis of esophageal carcinoma and control cells revealed 10 proteins that were upregulated. A further 10 proteins were downregulated. Among these 20 differentially expressed proteins, brain and reproductive organ-expressed (BRE) protein was identified as a potential tumor promoter. It was high expressed by the esophageal carcinoma cells, as confirmed by RT-PCR and immunoblotting. BRE has been reported to be a stress-responsive protein. To gain further insight into its function, BRE expression was silenced in esophageal carcinoma cells using BRE-specific small interference RNA. It was discovered that silencing BRE expression downregulated prohibitin expression, but upregulated tumor-suppressor p53 expression. Furthermore, cyclin A and CDK2 expressions were suppressed suggesting that BRE inhibited cell proliferation. These results implied that BRE plays a significant role in mediating antiapoptotic and proliferative responses in esophageal carcinoma cells.

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“…Due to its low mutation rate and essential function, PHB1 is a suitable drug target [ 30 , 31 ]. Flavaglines are a class of natural products isolated from the medicinal plant Aglaia , which exerts a unique anti-cancer activity by binding to PHB1/PHB2 [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo

Liu,

Zhang,

et al. 2023

J Exp Clin Cancer Res

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Background Castration-resistant prostate cancer (CRPC) is currently the main challenge for prostate cancer (PCa) treatment, and there is an urgent need to find novel therapeutic targets and drugs. Prohibitin (PHB1) is a multifunctional chaperone/scaffold protein that is upregulated in various cancers and plays a pro-cancer role. FL3 is a synthetic flavagline drug that inhibits cancer cell proliferation by targeting PHB1. However, the biological functions of PHB1 in CRPC and the effect of FL3 on CRPC cells remain to be explored. Methods Several public datasets were used to analyze the association between the expression level of PHB1 and PCa progression as well as outcome in PCa patients. The expression of PHB1 in human PCa specimens and PCa cell lines was examined by immunohistochemistry (IHC), qRT-PCR, and Western blot. The biological roles of PHB1 in castration resistance and underlying mechanisms were investigated by gain/loss-of-function analyses. Next, in vitro and in vivo experiments were conducted to investigate the anti-cancer effects of FL3 on CRPC cells as well as the underlying mechanisms. Results PHB1 expression was significantly upregulated in CRPC and was associated with poor prognosis. PHB1 promoted castration resistance of PCa cells under androgen deprivation condition. PHB1 is an androgen receptor (AR) suppressive gene, and androgen deprivation promoted the PHB1 expression and its nucleus-cytoplasmic translocation. FL3, alone or combined with the second-generation anti-androgen Enzalutamide (ENZ), suppressed CRPC cells especially ENZ-sensitive CRPC cells both in vitro and in vivo. Mechanically, we demonstrated that FL3 promoted trafficking of PHB1 from plasma membrane and mitochondria to nucleus, which in turn inhibited AR signaling as well as MAPK signaling, yet promoted apoptosis in CRPC cells. Conclusion Our data indicated that PHB1 is aberrantly upregulated in CRPC and is involved in castration resistance, as well as providing a novel rational approach for treating ENZ-sensitive CRPC.

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Prohibitin mutations are uncommon in prostate cancer families linked to chromosome 17q

Cited by 7 publications

References 15 publications

Fine-mapping the putative chromosome 17q21–22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis

Fine-mapping the putative chromosome 17q21–22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis

Comparative proteomic analysis reveals differentially expressed proteins regulated by a potential tumor promoter, BRE, in human esophageal carcinoma cells

Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo

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