HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prasad, K. N. Articles by Prasad, K. C. Search for Related Content PubMed PubMed Citation Articles by Prasad, K. N. Articles by Prasad, K. C.

---

MINIREVIEW

Differentiation Genes: Are They Primary Targets for Human Carcinogenesis?

Kedar N. Prasad^*,1, Alicia R. Hovland^*, Piruz Nahreini^*, William C. Cole^*, Peter Hovland^*, Bipin Kumar^* and K. Che Prasad

^* Center for Vitamins and Cancer Research, Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262; and
Department of Pathology, University of California, San Francisco Medical School, SanFrancisco, California 94131

In spite of extensive research in molecular carcinogenesis, genes that can be considered primary targets in human carcinogenesis remain to be identified. Mutated oncogenes or cellular growth regulatory genes, when incorporated into normal human epithelial cells, failed to immortalize or transform these cells. Therefore, they may be secondary events in human carcinogenesis. Based on some experimental studies we have proposed that downregulation of a differentiation gene may be the primary event in human carcinogenesis. Such a gene could be referred to as a tumor-initiating gene. Downregulation of a differentiation gene can be accomplished by a mutation in the differentiation gene, by activation of differentiation suppressor genes, and by inactivation of tumor suppressor genes. Downregulation of a differentiation gene can lead to immortalization of normal cells. Mutations in cellular proto-oncogenes, growth regulatory genes, and tumor suppressor genes in immortalized cells can lead to transformation. Such genes could be called tumor-promoting genes. This hypothesis can be documented by experiments published on differentiation of neuroblastoma (NB) cells in culture. The fact that terminal differentiation can be induced in NB cells by adenosine 3',5'-cyclic monophosphate (cAMP) suggests that the differentiation gene in these cells is not mutated, and thus can be activated by an appropriate agent. The fact that cAMP-resistant cells exist in NB cell populations suggests that a differentiation gene is mutated in these cancer cells, or that differentiation regulatory genes have become unresponsive to cAMP. In addition to cAMP, several other differentiating agents have been identified. Our proposed hypothesis of carcinogenesis can also be applied to other human tumors such as melanoma, pheochromocytoma, medulloblastoma, glioma, sarcoma, and colon cancer.

Key Words: differentiation genes • tumor suppressor genes • cellular oncogenes • viral oncogenes • telomerase • latent period

This article has been cited by other articles:

				J.-M. Yuan, Y.-T. Gao, C.-N. Ong, R. K. Ross, and M. C. Yu Prediagnostic level of serum retinol in relation to reduced risk of hepatocellular carcinoma. J Natl Cancer Inst, April 5, 2006; 98(7): 482 - 490. [Abstract] [Full Text] [PDF]

				K N Prasad Rationale for using multiple antioxidants in protecting humans against low doses of ionizing radiation Br. J. Radiol., June 1, 2005; 78(930): 485 - 492. [Abstract] [Full Text] [PDF]

				K. N. Prasad, W. C. Cole, and G. M. Hasse Health Risks of Low Dose Ionizing Radiation in Humans: A Review Experimental Biology and Medicine, May 1, 2004; 229(5): 378 - 382. [Abstract] [Full Text] [PDF]