Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis
Article first published online: 25 APR 2002
Copyright © 2002 American Cancer Society
Volume 94, Issue 9, pages 2393–2400, 1 May 2002
How to Cite
Nagpal, J. K., Mishra, R. and Das, B. R. (2002), Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer, 94: 2393–2400. doi: 10.1002/cncr.10499
- Issue published online: 25 APR 2002
- Article first published online: 25 APR 2002
- Manuscript Accepted: 3 DEC 2001
- Manuscript Revised: 17 NOV 2001
- Manuscript Received: 17 SEP 2001
- Department of Biotechnology, Government. of India. Grant Numbers: BT/R&D/091/066/96, BT/PR1347/HRD/15/131/98
- Council of Scientific and Industrial Research, Government of India
- squamous cell carcinoma of the head and neck (HNSCC);
- tobacco chewing;
The Jak/Stat signaling pathway transmits signals from many cytokines and growth factor receptors to target genes in the nucleus. Constitutive activation of Stat-3 recently has been observed in many tumor cells, and dysregulation of the Stat signaling pathway has been proposed to be implicated in malignant transformation. In the current study for the first time to the authors's knowledge, the expression of STAT-3 was analyzed in various stages and sites of squamous cell carcinoma of the head and neck (HNSCC).
Tissue samples from 90 patients of tobacco chewing-mediated HNSCC representing various stages, sites, and differentiation states were selected for studying STAT-3 protein and RNA expression. In vivo localization of STAT-3 was studied by immunohistochemistry of paraffin embedded sections. The presence of STAT-3 and its phophorylated and activated form pSTAT-3 was checked by Western blotting. mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis analysis was conducted by in situ ENA nick end labeling assay and hematoxylin and eosin staining.
Overall, 58.9% of HNSCC tumors showed very high Stat-3 protein accumulation, and 23.3% showed intermediate accumulation whereas 17.8% of HNSCC tumors were negative for Stat-3. No Stat-3 was detected in normal samples, and only one of eight premalignant lesions showed intermediate Stat-3 accumulation. On immunoblotting, very high protein accumulation was detected in T1 and T2 classification, moderate in T3 and T4 (P = 0.033, chi-square test), whereas no Stat-3 was detected in normal samples. Similar trend also was found in Stat-3 mRNA expression by RT-PCR analysis which was high in T1 and T2 (early stages), moderate in T3 and T4 (late stages), and no expression in normal samples. The mean apoptotic indices were 1.75, 1.88, and 1.66 for normal, premalignant lesions, and HNSCC cases, respectively.
Stat-3 activation is an early event in head and neck carcinogenesis though its role in blocking the apoptosis in vivo in solid tumors was not observed. Cancer 2002;94:2393–400. © 2002 American Cancer Society.