p53, p21, and cyclin d1 protein expression patterns in patients with breast cancer

Background and Aim: The mutation in the wild-type tumor suppressor gene p53 is the most common genetic change in human tumors. In addition, the normal function of p21, which is both antiproliferative and an inhibitor of the cell cycle, is disrupted in some types of cancer. Meanwhile, cyclin D1 is a member of the cyclin protein family that is involved in regulating cell cycle progression. This study aimed to assess the expressions of the cell cycle inhibitory proteins p21, cyclin D1, and tumor suppressor gene p53, as well as their influence on the expressed histopathological changes in breast cancer tissues. Materials and Methods: Overall, 40 breast tissue specimens were investigated in this study, 30 of which were cancerous, while 10 were healthy tissues. p53, p21, and cyclin D1 expression patterns were detected using an immunohistochemistry (IHC) system. Results: The IHC reactions for p53 were positively observed in 27/30 (90%) cancerous tissues, compared with 2/10 (20%) normal breast tissues. For p21, reactions were observed in 28/30 (93.33%) cancerous tissues and 3/10 (30%) control tissues. For cyclin D1, reactions were observed in 25/30 (83.33%) cancerous tissues and 1/10 (10%) control tissues. The differences between the breast cancer tissues and the control tissues were statistically highly significant (p<0.01). Conclusion: The high expression rates of p21, cyclin D1, and p53 in malignant breast cancer cells with little or no regulatory role might imply mutational events in these proteins operating in concert with a variety of other genetic mutations in these tissues, which may play a molecular role in the development and/or progression of breast carcinogenesis.

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DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERα-positive breast cancer cells

Breast Cancer Research and Treatment ◽

10.1007/s10549-015-3281-y ◽

2015 ◽

Vol 149 (3) ◽

pp. 693-703 ◽

Cited By ~ 8

Author(s):

Marleen Ansems ◽

Jonas Nørskov Søndergaard ◽

Anieta M. Sieuwerts ◽

Maaike W. G. Looman ◽

Marcel Smid ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Suppressor ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Tumor Suppressor Gene ◽

Breast Cancer Cells ◽

Suppressor Gene ◽

Cycle Arrest ◽

Positive Breast Cancer

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Tumor suppressor gene p16/INK4A/CDKN2A-dependent regulation into and out of the cell cycle in a spontaneous canine model of breast cancer

Journal of Cellular Biochemistry ◽

10.1002/jcb.24476 ◽

2013 ◽

Vol 114 (6) ◽

pp. 1355-1363 ◽

Cited By ~ 17

Author(s):

Payal Agarwal ◽

Maninder Sandey ◽

Patricia DeInnocentes ◽

R. Curtis Bird

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Canine Model ◽

Suppressor Gene ◽

P16 Ink4a

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The NF2 Tumor Suppressor Gene Product, Merlin, Inhibits Cell Proliferation and Cell Cycle Progression by Repressing Cyclin D1 Expression

Molecular and Cellular Biology ◽

10.1128/mcb.25.6.2384-2394.2005 ◽

2005 ◽

Vol 25 (6) ◽

pp. 2384-2394 ◽

Cited By ~ 119

Author(s):

Guang-Hui Xiao ◽

Ryan Gallagher ◽

Justin Shetler ◽

Kristine Skele ◽

Deborah A. Altomare ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Tumor Suppressor ◽

Cyclin D1 ◽

Tumor Suppressor Gene ◽

Promoter Activity ◽

Cell Cycle Progression ◽

Malignant Tumors ◽

Suppressor Gene ◽

Cycle Progression

ABSTRACT Inactivation of the NF2 tumor suppressor gene has been observed in certain benign and malignant tumors. Recent studies have demonstrated that merlin, the product of the NF2 gene, is regulated by Rac/PAK signaling. However, the mechanism by which merlin acts as a tumor suppressor has remained obscure. In this report, we show that adenovirus-mediated expression of merlin in NF2-deficient tumor cells inhibits cell proliferation and arrests cells at G1 phase, concomitant with decreased expression of cyclin D1, inhibition of CDK4 activity, and dephosphorylation of pRB. The effect of merlin on cell cycle progression was partially overridden by ectopic expression of cyclin D1. RNA interference experiments showed that silencing of the endogenous NF2 gene results in upregulation of cyclin D1 and S-phase entry. Furthermore, PAK1-stimulated cyclin D1 promoter activity was repressed by cotransfection of NF2, and PAK activity was inhibited by expression of merlin. Interestingly, the S518A mutant form of merlin, which is refractory to phosphorylation by PAK, was more efficient than the wild-type protein in inhibiting cell cycle progression and in repressing cyclin D1 promoter activity. Collectively, our data indicate that merlin exerts its antiproliferative effect, at least in part, via repression of PAK-induced cyclin D1 expression, suggesting a unifying mechanism by which merlin inactivation might contribute to the overgrowth seen in both noninvasive and malignant tumors.

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Gene Therapy for Head and Neck Cancer: Comparing the Tumor Suppressor Gene p53 and a Cell Cycle Regulator WAF1/CIP1 (p21)

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.1996.01890170025006 ◽

1996 ◽

Vol 122 (5) ◽

pp. 489-493 ◽

Cited By ~ 38

Author(s):

G. L. Clayman ◽

T.-J. Liu ◽

S. M. Overholt ◽

S. R. Mobley ◽

M. Wang ◽

...

Keyword(s):

Cell Cycle ◽

Gene Therapy ◽

Head And Neck Cancer ◽

Tumor Suppressor ◽

Head And Neck ◽

Tumor Suppressor Gene ◽

Neck Cancer ◽

Suppressor Gene ◽

A Cell ◽

Tumor Suppressor Gene P53

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Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽

10.3174/ng.2000003 ◽

2020 ◽

Vol 10 (4) ◽

pp. 228-235

Author(s):

S. Naganawa ◽

T. Donohue ◽

A. Capizzano ◽

Y. Ota ◽

J. Kim ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Soft Tissue Sarcomas ◽

Suppressor Gene ◽

Imaging Findings ◽

Li Fraumeni Syndrome ◽

Increased Risk ◽

Li Fraumeni ◽

Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

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