Table Of ContentTUMOR SUPPRESSOR
GENES
Edited by Yue Cheng
Tumor Suppressor Genes
Edited by Yue Cheng
Published by InTech
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First published February, 2012
Printed in Croatia
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Tumor Suppressor Genes, Edited by Yue Cheng
p. cm.
ISBN 978-953-307-879-3
Contents
Preface IX
Chapter 1 Tumor Suppressor Gene p16/INK4A/CDKN2A
and Its Role in Cell Cycle Exit, Differentiation,
and Determination of Cell Fate 1
Payal Agarwal, Farruk Mohammad Lutful Kabir,
Patricia DeInnocentes and Richard Curtis Bird
Chapter 2 Susceptibility of Epithelium to
PTEN-Deficient Tumorigenesis 35
Chun-Ming Chen, Tsai-Ling Lu, Fang-Yi Su and Li-Ru You
Chapter 3 Identification of Tumor Suppressor Genes
via Cell Fusion and Chromosomal Transfer 53
Hong Lok Lung, Arthur Kwok Leung Cheung,
Josephine Mun Yee Ko, Yue Cheng and Maria Li Lung
Chapter 4 TP53 Gene Polymorphisms in Cancer Risk:
The Modulating Effect of Ageing, Ethnicity
and TP53 Somatic Abnormalities 79
Evgeny V. Denisov, Nadezhda V. Cherdyntseva,
Nicolay V. Litviakov, Elena A. Malinovskaya, Natalya N. Babyshkina,
Valentina A. Belyavskaya and Mikhail I. Voevoda
Chapter 5 Epigenetics and Tumor Suppressor Genes 111
MingZhou Guo, XueFeng Liu and WeiMin Zhang
Chapter 6 Therapeutic Targeting of p53-Mediated Apoptosis
Pathway in Head and Neck Squamous Cell Carcinomas:
Current Progress and Challenges 129
Solachuddin Jauhari Arief Ichwan, Muhammad Taher Bakhtiar,
Kiyoshi Ohtani and Masa-Aki Ikeda
Chapter 7 Signaling Mechanisms of Transforming Growth
Factor-β (TGF-β) in Cancer: TGF-β Induces Apoptosis
in Lung Cells by a Smad-Dependent Mechanism 145
Mi Jung Lim, Tiffany Lin and Sonia B. Jakowlew
VI Contents
Chapter 8 Refining the Role of Lgl, Dlg and Scrib
in Tumor Suppression and Beyond:
Learning from the Old Time Classics 181
Fani Papagiannouli and Bernard M. Mechler
Chapter 9 Epigenetic and Posttranscriptional Alterations of Tumor
Suppressor Genes in Sporadic Pituitary Adenomas 221
Henriett Butz, Károly Rácz and Attila Patócs
Chapter 10 Genomic and Expression Alterations of
Tumor Suppressor Genes in Meningioma
Development, Progression and Recurrence 247
E. Pérez-Magán, J.A. Rey, B. Meléndez and Javier S. Castresana
Chapter 11 Control of Retinal Development
by Tumor Suppressor Genes 269
Robert Cantrup, Gaurav Kaushik and Carol Schuurmans
Chapter 12 Properties of Human Tumor Suppressor
101F6 Protein as a Cytochrome b561 and
Its Preliminary Crystallization Trials 295
Mariam C. Recuenco, Suguru Watanabe,
Fusako Takeuchi, Sam-Yong Park and Motonari Tsubaki
Chapter 13 Epigenetic Control of
Tumor Suppressor Genes in Lung Cancer 309
Xuan Qiu, Roman Perez-Soler and Yiyu Zou
Preface
Tumor suppressor genes (TSGs) play critical roles in many biological processes,
including cell cycle control, apoptosis, DNA repair, cell division and differentiation,
tumor migration and metastasis, and reprogramming control of somatic cells. TSGs
were named so because of their functional roles in original tumor growth control
experiments.
Early somatic cell fusion studies of malignant and nonmalignant cell provided the first
evidence of a class of negatively acting TSGs, harbored on normal chromosomes that
contrast to dominant-acting oncogenes, which play important roles in tumor
suppression. The first TSG was isolated from retinoblastoma, although recent evidence
has suggested that this gene is also a key regulator of normal developmental events, as
addressed in this book. Other important TSGs, such as P53, P16 and PTEN, were
subsequently identified based on “two-hit” hypothesis of TSGs as well.
Underlying mechanisms of TSGs have been vigorously investigated over the past 30
years. This book covers the aspects of most fascinating fields, from cell cycle control,
signaling pathways, gene dosage effects and epigenetic control of gene expression, to
current challenges and future directions in TSG studies. Since tumor suppression is now
a huge research field and many novel TSGs have been identified from various human
malignancies, it is almost impossible to cover all interesting areas in just one book.
As a classic TSG, P53 is addressed in this book because of its risk on polymorphism
and its critical role in apoptosis pathways. P16 and its family that regulate cell cycle
and determine cell fate are introduced and reviewed in detail. Some of the chapters
focus on the epigenetic control of TSG, notably P16, in lung, pituitary tumors and
meningioma. TSG studies in other models, such as transgenic mouse and Drosophila,
are also included in this book. Studies on PTEN and other classic TSGs are described
in these chapters well. The regulation of an important cellular signaling, TGF-beta, in
lung cancer is presented in this book, and readers can find information on other
signaling controls of carcinogenesis in different chapters. Furthermore, expression and
purification of the human 101F6 protein, encoded by a candidate TSG on the
chromosome 3p21.3, is presented as a crystallization trial example. Finally, one chapter
discusses a classic approach using cell fusion and chromosome transfer to identify
novel TSGs in nasopharyngeal carcinoma.
X Preface
A wide range of basic, translational, and clinical researches is leading the quest to find
promising new ways to use these genes to suppress cancer. An example of such trails
in head and neck cancer is presented in this book. Although we are not there yet,
ongoing research efforts on TSGs, coupled with advances in gene therapy and other
techniques, have the potential to open new avenues in the treatment of human tumors.
We hope that this book will be helpful to both researchers and clinicians.
Yue Cheng, PhD
The University of Hong Kong
China
