Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Maiti, Guru Prasad; Ghosh, Amlan; Chatterjee, Ramdas; Roy, Anup; Sharp, Tyson V.; Roychoudhury, Susanta; Panda, Chinmay Kumar

doi:10.7314/apjcp.2012.13.9.4341

Cited by 11 publications

(10 citation statements)

References 21 publications

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“…Expression of the tumor suppressor LIMD1 throughout the normal-cervix is indicative of its role in maintaining normal cell homeostasis. Similar pattern of LIMD1 expression was observed in normal oral epithelium (21). VHL expression is lower in the basal-parabasal layers of normalcervix compared to the spinous layer, suggesting it may have a critical role in cellular differentiation and proliferation.…”

Section: Discussionsupporting

confidence: 69%

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Deregulation of LIMD1–VHL–HIF-1α–VEGF pathway is associated with different stages of cervical cancer

Chakraborty

Mitra

Roychowdhury

et al. 2018

Biochemical Journal

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To understand the mechanism of cellular stress in basal-parabasal layers of normal cervical epithelium and during different stages of cervical carcinoma, we analyzed the alterations (expression/methylation/copy number variation/mutation) of HIF-1α and its associated genes LIMD1, VHL and VEGF in disease-free normal cervix ( = 9), adjacent normal cervix of tumors ( = 70), cervical intraepithelial neoplasia (CIN; = 32), cancer of uterine cervix (CACX; = 174) samples and two CACX cell lines. In basal-parabasal layers of normal cervical epithelium, LIMD1 showed high protein expression, while low protein expression of VHL was concordant with high expression of HIF-1α and VEGF irrespective of HPV-16 (human papillomavirus 16) infection. This was in concordance with the low promoter methylation of LIMD1 and high in VHL in the basal-parabasal layers of normal cervix. LIMD1 expression was significantly reduced while VHL expression was unchanged during different stages of cervical carcinoma. This was in concordance with their frequent methylation during different stages of this tumor. In different stages of cervical carcinoma, the expression pattern of HIF-1α and VEGF was high as seen in basal-parabasal layers and inversely correlated with the expression of LIMD1 and VHL. This was validated by demethylation experiments using 5-aza-2'-deoxycytidine in CACX cell lines. Additional deletion of LIMD1 and VHL in CIN/CACX provided an additional growth advantage during cervical carcinogenesis through reduced expression of genes and associated with poor prognosis of patients. Our data showed that overexpression of HIF-1α and its target gene VEGF in the basal-parabasal layers of normal cervix was due to frequent inactivation of VHL by its promoter methylation. This profile was maintained during different stages of cervical carcinoma with additional methylation/deletion of VHL and LIMD1.

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Section: Discussionsupporting

confidence: 69%

“…significant increase in methylation frequency of the LIMD1and VHL genes during stage-wise development of this tumor. Similar pattern of expression and methylation of LIMD1 was reported during development of HNSCC from normal oral epithelium(20,21). Likewise, low expression profile of VHL was reported in normal-cervix and CACX(8).…”

supporting

confidence: 74%

Deregulation of LIMD1–VHL–HIF-1α–VEGF pathway is associated with different stages of cervical cancer

Chakraborty

Mitra

Roychowdhury

et al. 2018

Biochemical Journal

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“…As a result, there was hyperphosphorylation of RB for progression of the cell cycle. On the other hand, inactivation of MLH1, a DNA repair protein and p53 occurred at mild dysplastic stage, indicating the impairment of DNA repair as an early event in the development of the tumor (Maiti et al, 2012). Bcl2, an anti-apoptotic protein, shows decrease in expression from mild dysplasia (Loro et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

Sarkar

Maiti²,

Jha³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/ pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

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“…-While normal tissues expressed the larger RBSP3 B form, tumors either showed no expression of RBSP3, or preferentially expressed the smaller, less active form, RBSP3 A (Ghosh et al, 2010). Expression of RBSP3 decreases from pre-malignant to malignant lesions (Maiti et al, 2012). Expression of RBSP3 was seen to be increased from pre-neoadjuvant chemotherapy tumors to post-therapy tumors (Sarkar et al, 2013).…”

Section: Head and Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 91%

“…Oncogenesis Early alteration of RBSP3 takes place in head and neck cancers (Ghosh et al, 2010). Loss of expression of RBSP3 was seen to be required for progression from malignant to invasive cancer (Maiti et al, 2012). Regain of expression of RBSP3 in post-therapy tumors may be one of the reasons of shrinkage of tumors due to neoadjuvant chemotherapy (Sarkar et al, 2013).…”

Section: Head and Neck Squamous Cell Carcinoma (Hnscc)mentioning

confidence: 99%

CTDSPL (CTD (Carboxy-Terminal Domain, RNA Polymerase II, Polypeptide A) Small Phosphatase-Like)

Sarkar¹,

Maiti²,

Panda³

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Cited by 11 publications

References 21 publications

Deregulation of LIMD1–VHL–HIF-1α–VEGF pathway is associated with different stages of cervical cancer

Deregulation of LIMD1–VHL–HIF-1α–VEGF pathway is associated with different stages of cervical cancer

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

CTDSPL (CTD (Carboxy-Terminal Domain, RNA Polymerase II, Polypeptide A) Small Phosphatase-Like)

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