Expression of the Ca[sup 2+]-Activated Chloride Channel Genes CLCA1 and CLCA2 Is Downregulated in Human Colorectal Cancer

Bustin, Stephen A.; Li, Shu-Rui; Dorudi, Sina
June 2001
DNA & Cell Biology;Jun2001, Vol. 20 Issue 6, p331
Academic Journal
The role of ion channels in carcinogenesis and tumor progression remains unclear. We have used suppression subtractive hybridization of mRNA from paired normal colon epithelium and tumor, followed by quantitative kinetic RT-PCR, to demonstrate that the transcription of two members of a novel Ca[sup 2+]-dependent chloride channel family, CLCA1 and CLCA2, was significantly downregulated in approximately 80% of colorectal carcinomas. This figure rose to >90% when expression was adjusted for tumor cell proliferation. In normal colon epithelium, CLCA1 mRNA levels were significantly associated with c-myc transcription but became decoupled in the tumor samples. There was no association between CLCA2 and either CLCA1 or c-myc mRNA levels. Transcription of both genes in three colorectal cancer cell lines, T84, HT29, and Caco2, was barely detectable. Illegitimate transcription of CLCA1 was detected in 12 of 15 blood samples taken from healthy volunteers, making its use as a marker for the detection of tumor spread unreliable. Our results suggest that CLCA1 could specify a new tumor suppressor and that, as in breast cancer, CLCA2 may function as a tumor suppressor in colorectal cancer.


Related Articles

  • Beta-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Tetsu, Osamu; McCormick, Frank // Nature;4/1/1999, Vol. 398 Issue 6726, p422 

    Presents research which showed that beta-catenin activates transcription from the cyclin D1 promoter in human colon cancer. Role of mutations in the adenomatous polyposis coli (APC) tumor-suppressor gene; Effects of the accumulation of beta-catenin from the loss of APC on neoplastic...

  • Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation. Jiang, Zhonghua; Su, Dongming; Wang, Xiaohong; Liu, Li; He, Xiaolu; Tan, Xueming; Fan, Zhining; Wang, Xiang; Ma, Limei // Molecular & Cellular Biochemistry;Oct2015, Vol. 408 Issue 1/2, p205 

    Derlin-1 is overexpressed in many types of solid tumors and plays an important role in cancer progression. However, the expression pattern and functions of Derlin-1 in human colon cancer are not fully understood. In the present study, we examined Derlin-1 expression in colon cancer cell lines...

  • P-0280GAMMA H2AX AND 53BP1, THE MARKERS OF DNA DOUBLE STRAND BREAK ARE ASSOCIATED WITH DEVELOPING ADENOMA AND ADENOCARCINOMA IN COLON. Kim, Jeong Ho; Jeon, Joon Han; Kim, Hye Kang; Cho, Hyung Jun; Cheung, Dae Young; Kim, Jin Il; Kim, Hyun Jin; Lee, Seong Jin; Lee, Hyun Jeong; Cho, Se Hyun; Kim, Jae Kwang; Park, Soo-Heon // Annals of Oncology;Jun2013, Vol. 24 Issue suppl_4, piv114 

    No abstract available.

  • Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation. Shu Yang; Bo Wu; Haimei Sun; Fengqing Ji; Tingyi Sun; Yan Zhao; Deshan Zhou // Bioscience Reports;Feb2016, Vol. 36 Issue 1, p1 

    Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be...

  • CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. McCleland, Mark L.; Mesh, Kathryn; Lorenzana, Edward; Chopra, Vivek S.; Segal, Ehud; Watanabe, Colin; Haley, Benjamin; Mayba, Oleg; Yaylaoglu, Murat; Gnad, Florian; Firestein, Ron // Journal of Clinical Investigation;Feb2016, Vol. 126 Issue 2, p639 

    Colon tumors arise in a stepwise fashion from either discrete genetic perturbations or epigenetic dysregulation. To uncover the key epigenetic regulators that drive colon cancer growth, we used a CRISPR loss-of-function screen and identified a number of essential genes, including the bromodomain...

  • Identification of Unique miRNA Biomarkers in Colorectal Adenoma and Carcinoma Using Microarray: Evaluation of Their Putative Role in Disease Progression. Narasimhan, Kothandaraman; Gauthaman, Kalamegam; Pushparaj, Peter Natesan; Meenakumari, Govindasamy; Ahmed Chaudhary, Adeel Gulzar; Abuzenadah, Adel; Gari, Mamdooh Abdullah; Al Qahtani, Mohammed; Manikandan, Jayapal // ISRN Otolaryngology;2014, p1 

    MicroRNAs (miRNAs) are known to be dysregulated and play a key role in cancer progression. The present study aims to identify the miRNAs associated with colorectal adenoma and carcinoma to evaluate their role in tumor progression and metastasis using microarray. In silico analysis of miRNAs was...

  • Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells. John Huang; Mei-Ieng Che; Yu-Ting Huang; Ming-Kwang Shyu; Yu-Ming Huang; Yao-Ming Wu; Wei-Chou Lin; Pei-Hsin Huang; Jin-Tung Liang; Po-Huang Lee; Min-Chuan Huang // Carcinogenesis;Aug2009, Vol. 30 Issue 8, p1452 

    Mucins play a key role in tumorigenesis. MUC15 is a membrane-bound mucin and the MUC15 messenger RNA (mRNA) has been detected in various organs. However, its role in tumor malignancy is still unclear. This study was to investigate the MUC15 expression in colorectal tumors and the role of MUC15...

  • Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice. Bi, Xiuli; Pohl, Nicole M.; Qian, Zhibin; Yang, George R.; Gou, Yuan; Guzman, Grace; Kajdacsy-Balla, Andre; Iozzo, Renato V.; Yang, Wancai // Carcinogenesis;Feb2012, Vol. 33 Issue 2, p326 

    Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27kip1 and E-cadherin and an...

  • Co-targeting of Cyclooxygenase-2 and FoxM1 is a viable strategy in inducing anticancer effects in colorectal cancer cells. Ahmed, Maqbool; Hussain, Azhar R.; Siraj, Abdul K.; Uddin, Shahab; Al-Sanea, Nasser; Al-Dayel, Fouad; Al-Assiri, Mohammed; Beg, Shaham; Al-Kuraya, Khawla S. // Molecular Cancer;Jul2015, Vol. 14 Issue 1, p1 

    Background: Cross-talk between deregulated signaling pathways in cancer cells causes uncontrolled growth and proliferation. These cancers cells become more aggressive and quickly develop resistance to therapy. Therefore targeting of these deregulated pathways simultaneously can result in...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics