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Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, Nakatani Y - Cancer Sci. (2015)

Bottom Line: Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns.GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors.The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

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Glycoprotein non-metastatic B (GPNMB) expression in Birt–Hogg–Dubé (BHD) and sporadic tumors. (a) Expression levels of GPNMB mRNA were analyzed by quantitative RT-PCR as shown. Sporadic renal tumors include clear cell renal cell carcinomas (RCCs) (n = 9), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 6). (b) Representative results of Western blot analysis of BHD kidneys. Patients BHD9 and BHD17 had two independent tumors (T1, T2), respectively. Two isoforms (115 kDa and 80 kDa) of GPNMB bands were seen in tumor lanes, but not in normal-looking lanes. N, normal-looking region; T, tumor region. (c) Representative results of Western blot analysis of sporadic renal tumors and normal kidneys without the background of BHD. GPNMB bands were barely seen in sporadic tumor and normal kidney lanes. Sporadic renal tumors included clear cell RCCs (n = 3), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 4). PC, positive control using BHD9-T2.
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fig05: Glycoprotein non-metastatic B (GPNMB) expression in Birt–Hogg–Dubé (BHD) and sporadic tumors. (a) Expression levels of GPNMB mRNA were analyzed by quantitative RT-PCR as shown. Sporadic renal tumors include clear cell renal cell carcinomas (RCCs) (n = 9), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 6). (b) Representative results of Western blot analysis of BHD kidneys. Patients BHD9 and BHD17 had two independent tumors (T1, T2), respectively. Two isoforms (115 kDa and 80 kDa) of GPNMB bands were seen in tumor lanes, but not in normal-looking lanes. N, normal-looking region; T, tumor region. (c) Representative results of Western blot analysis of sporadic renal tumors and normal kidneys without the background of BHD. GPNMB bands were barely seen in sporadic tumor and normal kidney lanes. Sporadic renal tumors included clear cell RCCs (n = 3), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 4). PC, positive control using BHD9-T2.

Mentions: Western blotting clearly indicated the loss of FLCN, but immunostaining for FLCN was not sufficiently specific to predict RCC associated with BHD. Some auxiliary markers were desirable to give an indication for genetic analysis. In the current study, we compared GPNMB expression between BHD and sporadic tumors. In quantitative RT-PCR, RCCs from BHD patients expressed GPNMB mRNA at levels that averaged 23-fold higher compared to sporadic RCCs (P < 0.01, Student's t-test) (Fig.5a). GPNMB mRNA levels of non-neoplastic renal tissues of BHD patients were as low as those of sporadic RCCs (data not shown).


Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, Nakatani Y - Cancer Sci. (2015)

Glycoprotein non-metastatic B (GPNMB) expression in Birt–Hogg–Dubé (BHD) and sporadic tumors. (a) Expression levels of GPNMB mRNA were analyzed by quantitative RT-PCR as shown. Sporadic renal tumors include clear cell renal cell carcinomas (RCCs) (n = 9), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 6). (b) Representative results of Western blot analysis of BHD kidneys. Patients BHD9 and BHD17 had two independent tumors (T1, T2), respectively. Two isoforms (115 kDa and 80 kDa) of GPNMB bands were seen in tumor lanes, but not in normal-looking lanes. N, normal-looking region; T, tumor region. (c) Representative results of Western blot analysis of sporadic renal tumors and normal kidneys without the background of BHD. GPNMB bands were barely seen in sporadic tumor and normal kidney lanes. Sporadic renal tumors included clear cell RCCs (n = 3), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 4). PC, positive control using BHD9-T2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376441&req=5

fig05: Glycoprotein non-metastatic B (GPNMB) expression in Birt–Hogg–Dubé (BHD) and sporadic tumors. (a) Expression levels of GPNMB mRNA were analyzed by quantitative RT-PCR as shown. Sporadic renal tumors include clear cell renal cell carcinomas (RCCs) (n = 9), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 6). (b) Representative results of Western blot analysis of BHD kidneys. Patients BHD9 and BHD17 had two independent tumors (T1, T2), respectively. Two isoforms (115 kDa and 80 kDa) of GPNMB bands were seen in tumor lanes, but not in normal-looking lanes. N, normal-looking region; T, tumor region. (c) Representative results of Western blot analysis of sporadic renal tumors and normal kidneys without the background of BHD. GPNMB bands were barely seen in sporadic tumor and normal kidney lanes. Sporadic renal tumors included clear cell RCCs (n = 3), oncocytoma (n = 1), papillary RCC (n = 1), and chromophobe RCCs (n = 4). PC, positive control using BHD9-T2.
Mentions: Western blotting clearly indicated the loss of FLCN, but immunostaining for FLCN was not sufficiently specific to predict RCC associated with BHD. Some auxiliary markers were desirable to give an indication for genetic analysis. In the current study, we compared GPNMB expression between BHD and sporadic tumors. In quantitative RT-PCR, RCCs from BHD patients expressed GPNMB mRNA at levels that averaged 23-fold higher compared to sporadic RCCs (P < 0.01, Student's t-test) (Fig.5a). GPNMB mRNA levels of non-neoplastic renal tissues of BHD patients were as low as those of sporadic RCCs (data not shown).

Bottom Line: Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns.GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors.The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Show MeSH
Related in: MedlinePlus