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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Pathological characterization of Kank in renal cell carcinoma
Badal Chandra Roy1, Teiichiro Aoyagi, Shubhashish Sarkar
1Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Abstract:
The Kank gene was found as a candidate tumor suppressor gene at 9p24 by loss-of-heterozygosity search in renal cell carcinoma (RCC) and seems to have a role in controlling the formation of the cytoskeleton through the polymerization of actin. Here, we characterized the Kank protein in renal tubular cells as well as other glandular cells in the colon, stomach, prostate, testis, pancreas, thyroid, uterus, submandibular gland, adrenal, duodenum, and esophagus, and specific cells such as hepatic, alveolar myocardial, and glial cells by using a monoclonal antibody against Kank. Loss of expression of Kank in one RCC sample was detected by immunohistochemical and Western blot analyses while expression of CDKN2A (p16/Ink4A) was retained in the sample. The expression of Kank in the cytoplasm and at the sites of membrane ruffling in HEK293 and VMRC-RCW cells and in a primary culture of renal tubular cells was also detected by fluorescence-based immunostaining.
Insights
The Kank protein, a potential tumor suppressor, is expressed in various human cells, including renal tubular cells. Its loss of expression in one renal cell carcinoma (RCC) sample suggests a role in cancer development.
Area of Science:
- Oncology
- Cell Biology
- Molecular Genetics
Background:
- The Kank gene, identified at 9p24, is a candidate tumor suppressor gene implicated in renal cell carcinoma (RCC).
- Kank protein is hypothesized to regulate cytoskeleton formation via actin polymerization.
Purpose of the Study:
- To characterize the expression and localization of Kank protein in various human cell types.
- To investigate the expression status of Kank in a renal cell carcinoma (RCC) sample with retained CDKN2A (p16/Ink4A) expression.
Main Methods:
- Monoclonal antibody against Kank used for immunohistochemical analysis.
- Western blot analysis to assess Kank protein levels.
- Fluorescence-based immunostaining to determine subcellular localization.
Main Results:
- Kank protein expression was characterized in diverse cell types including renal tubular, glandular (colon, stomach, prostate, etc.), hepatic, myocardial, and glial cells.
- Loss of Kank expression was observed in one RCC sample, while CDKN2A (p16/Ink4A) expression remained intact.
- Kank expression was detected in the cytoplasm and membrane ruffling sites of HEK293, VMRC-RCW, and primary renal tubular cells.
Conclusions:
- Kank protein is expressed in a wide range of human cells, supporting its potential broad biological functions.
- Loss of Kank expression in RCC, independent of CDKN2A, highlights its potential role as a tumor suppressor in kidney cancer.
- Kank protein's localization at membrane ruffling sites suggests involvement in cellular dynamics and cytoskeleton regulation.
