Immunohistochemical study of cell cycle modulators in G1-S transition in clinical breast cancer tissue

Ito, Yasuhiro; Kobayashi, Tetsuro; Takeda, Tsutomu; Komoike, Yoshifumi; Wakasugi, E; Tamaki, Yasuhiro; Umeshita, Koji; Monden, Takushi; Monden, Morito

doi:10.1007/bf02966969

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…MCF-7 cells, on the other hand, gave no p i6 signal as was reported pre viously [7,15]. The specificity of anti-pRB and anti-cdk4 antibodies has already been confirmed in previous studies in our department [20,22], pRB was often heterogeneously expressed in duct-epi thelial cells in normal mammary glands. cdk4 and p i6 expression in normal mammary glands was restricted in terms of both positivity and intensity so that they should be classified as negative.…”

Section: Resultssupporting

confidence: 66%

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Expression of p16 and Cyclin-Dependent Kinase 4 Proteins in Primary Breast Carcinomas

Ito

Kobayashi²,

Takeda³

et al. 1997

Oncology

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The immunolocalization of the pl6 and cdk4 proteins was investigated in 65 retinoblastoma gene product (pRB)-positive and 20 pRB-negative breast carcinomas. These proteins were expressed in similar lesions in 84.6% of the pRB-positive and 100% of the pRB-negative carcinomas. Diffuse expression of pl6 was observed in 73.8 and 70.0% of the pRB-positive and -negative cases, respectively. cdk4 and p 16 expression was significantly more heterogeneous in tumors of larger sizes and/or at higher stages. These findings suggest that p 16 can be induced regardless of pRB status and Rb gene function in primary breast carcinoma and that it modulates the cell cycle progression in association with cdk4.

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Section: Resultssupporting

confidence: 66%

“…The avidin-biotin-peroxidase complex technique, described elsewhere [20,21 ], was used in this study. Briefly, the tissues were rchydrated through a graded ethanol series ranging from 100 to 60%.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of p16 and Cyclin-Dependent Kinase 4 Proteins in Primary Breast Carcinomas

Ito

Kobayashi²,

Takeda³

et al. 1997

Oncology

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“…The transcriptional regulation of CDK4 expression in normal versus cancer cells has not been thoroughly studied. Yet there is ample evidence for increased expression in cancer, especially breast cancer (Ito et al, 1996;Sasano et al, 1997;An et al, 1999). Here, we investigated the role of bHLH transcription factors in CDK4 expression in mammary epithelial cells using a combination of overexpression, dominant-negative mutant, and chromatin immunoprecipitation (ChIP) methods.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a cancer-specific switch at the CDK4 promoter with loss of control by both USF and c-Myc

et al. 2004

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USF and c-Myc are basic helix-loop-helix transcription factors with similar DNA-binding specificities, but antagonistic effects on cellular transformation. In order to determine how these opposite functions correlate with the transcriptional activities of the two factors on particular downstream targets, we investigated the roles of USF and c-Myc in expression of CDK4, a known direct target of cMyc. Overexpression of either c-Myc or USF2, but not USF1, stimulated the expression of CDK4 promoterdriven reporter genes in the non-tumorigenic mammary epithelial MCF-10A cells. Dominant-negative mutants specific to either Myc or USF family proteins inhibited reporter gene activity as well as endogenous CDK4 expression, demonstrating involvement of both USF and Myc in CDK4 transcriptional control. In contrast, in two different breast cancer cell lines where USF is transcriptionally inactive and c-Myc is overexpressed, CDK4 promoter activity was no longer responsive to either transcription factor. Accordingly, chromatin immunoprecipitation revealed significantly lower levels of both USF and c-Myc bound to the endogenous CDK4 promoter in breast cancer cells than in MCF-10A cells, with a concomitant decrease in associated histone H3 acetylation. These results suggest that a major switch in the transcriptional control of CDK4 occurs during breast carcinogenesis, with likely alteration of cell cycle regulation.

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“…4A). The cyclin D:CDK4/6 complex is a factor that promotes breast cancer progression [23,24], and CDK4/6 inhibitors have recently been administered to patients with unresectable or recurrent Luminal breast cancer [25,26]. The cyclin E:CDK2 complex has been reported to be involved in breast cancer progression [27,28].…”

Section: Pathway Analyses Of C1orf50 In Luminal a Breast Cancermentioning

confidence: 99%

The Role of C1orf50 in Breast Cancer Progression and Prognosis

Otani,

Tanaka,

Maekawa

et al. 2024

Preprint

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Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50 involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer.

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Immunohistochemical study of cell cycle modulators in G1-S transition in clinical breast cancer tissue

Cited by 4 publications

References 55 publications

Expression of p16 and Cyclin-Dependent Kinase 4 Proteins in Primary Breast Carcinomas

Expression of p16 and Cyclin-Dependent Kinase 4 Proteins in Primary Breast Carcinomas

Evidence for a cancer-specific switch at the CDK4 promoter with loss of control by both USF and c-Myc

The Role of C1orf50 in Breast Cancer Progression and Prognosis

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