Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer

Zhiwen Chen1, Jin Yang, Gan Wang

  • 1Urology Institute of People's Liberation Army, Southwest Hospital, The Third Military Medical University, Chongqing, P.R. China. zhiwen@mail.tmmu.com.cn

Cancer Research
|May 19, 2007
PubMed

Insights

Xeroderma pigmentosum group C (XPC) protein deficiency correlates with bladder cancer progression and drug resistance. Restoring XPC levels in cancer cells enhances DNA repair and chemotherapy-induced apoptosis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Xeroderma pigmentosum group C (XPC) is a key DNA damage recognition protein involved in DNA repair, cell cycle checkpoints, and apoptosis.
  • XPC defects are linked to various solid tumors, but its precise role in cancer progression remains largely unknown.

Purpose of the Study:

  • To investigate the correlation between XPC protein expression and bladder cancer progression.
  • To elucidate the role of XPC in DNA repair, drug resistance, and apoptosis in bladder cancer cells.

Main Methods:

  • Immunohistochemical analysis of XPC expression in bladder cancer tissues.
  • Assessment of DNA repair capacity and cisplatin resistance in HT1197 bladder cancer cells with varying XPC levels.
  • Stable transfection of XPC cDNA into HT1197 cells to restore XPC expression.

Main Results:

  • A strong correlation was observed between attenuated XPC protein expression and bladder cancer progression.
  • XPC deficiency was associated with p53 mutations and higher tumor malignancy.
  • HT1197 cells with low XPC showed reduced DNA repair and cisplatin resistance, which was reversed upon XPC restoration.
  • Restored XPC expression increased cisplatin-induced apoptosis and p53/p73 responses.

Conclusions:

  • XPC deficiency is a significant factor in bladder tumor progression and contributes to drug resistance in bladder cancer cells.
  • XPC plays a crucial role in maintaining DNA repair efficiency and chemosensitivity in bladder cancer.

Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...