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The protein encoded by the ERBB2 gene functions primarily as a transcription factor within the cell nucleus.
Answer: False
The protein encoded by the ERBB2 gene functions as a receptor tyrosine kinase located in the cell membrane, not as a transcription factor within the nucleus.
HER2 is a synonym for the ERBB2 gene product, and it is also known as CD340.
Answer: True
The ERBB2 gene product is known by multiple aliases, including HER2 and CD340, reflecting its various historical discoveries and functional contexts.
The name HER2 originates from its structural similarity to the human epidermal growth factor receptor 2 (HER2).
Answer: False
The name HER2 originates from its structural similarity to HER1 (Epidermal Growth Factor Receptor), not from similarity to itself.
The alias 'Neu' for HER2 comes from its discovery in a human brain tumor.
Answer: False
The alias 'Neu' for HER2 originates from its discovery in a rodent glioblastoma cell line, not a human brain tumor.
The ErbB-2 alias is derived from its resemblance to the avian erythroblastosis oncogene B, which codes for EGFR.
Answer: True
The alias ErbB-2 is derived from its homology to the avian erythroblastosis oncogene B (ErbB), which encodes the Epidermal Growth Factor Receptor (EGFR).
The molecular cloning of HER3 confirmed that HER2, Neu, and ErbB-2 are distinct genes.
Answer: False
The molecular cloning of EGFR, not HER3, confirmed that HER2, Neu, and ErbB-2 refer to the same gene, not distinct ones.
The ERBB2 gene is located on the short arm of human chromosome 17.
Answer: False
The ERBB2 gene is located on the long arm (q arm) of human chromosome 17, specifically at the 17q12 band, not the short arm.
According to the GRCh38 reference genome, the ERBB2 gene spans from base pair 39,687,914 to 39,730,426 on chromosome 17.
Answer: True
The ERBB2 gene is located between base pair 39,687,914 and 39,730,426 on human chromosome 17 according to the GRCh38 reference genome.
In mice, the ERBB2 gene is located on chromosome 11.
Answer: True
The ERBB2 gene is located on chromosome 11 in mice, specifically within the 11 D band.
HER2 belongs to the human epidermal growth factor receptor family, which includes EGFR, HER3, and HER4.
Answer: True
HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family, which comprises EGFR (HER1), HER3, and HER4.
HER2/neu is known to interact with proteins like beta-catenin (CTNNB1) and GRB2.
Answer: True
HER2/neu has been documented to interact with various intracellular proteins, including beta-catenin (CTNNB1) and GRB2, which are involved in signaling pathways.
PDB entry 1n8z illustrates the structure of HER2 bound to the antibody Herceptin.
Answer: True
PDB entry 1n8z represents the crystal structure of the extracellular domain of human HER2 in complex with the Fab fragment of Herceptin (Trastuzumab).
PDB entry 1s78 shows the structure of the HER2 protein alone, without any interacting molecules.
Answer: False
PDB entry 1s78 illustrates the structure of the HER2 protein in complex with the antibody Pertuzumab, not the protein in isolation.
The ERBB family receptors are primarily involved in regulating blood pressure.
Answer: False
The ERBB family receptors are primarily involved in regulating cellular processes such as growth, differentiation, and survival, not blood pressure.
CD designations are used to identify cell surface markers recognized by antibodies.
Answer: True
The Cluster of Differentiation (CD) designation serves to identify specific cell surface markers that are recognized by antibodies, aiding in cell classification.
The enzyme commission number for HER2 is 2.7.10.1, indicating it is a protein tyrosine kinase.
Answer: True
The enzyme commission number 2.7.10.1 correctly identifies HER2 as a protein tyrosine kinase, reflecting its enzymatic activity.
A gene designated as a 'proto-oncogene' can contribute to cancer when mutated or over-expressed.
Answer: True
Proto-oncogenes are normal cellular genes that, upon mutation, amplification, or translocation, can promote cancer development, acting as oncogenes.
The PDB entry 2a91 provides structural details of the intracellular kinase domain of HER2.
Answer: False
PDB entry 2a91 provides structural details of the extracellular domains of the ErbB2 protein, not its intracellular kinase domain.
The ERBB2 gene is located at band 17q12 on the human chromosome.
Answer: True
The ERBB2 gene is precisely mapped to band 17q12 on the long arm of human chromosome 17.
What is the primary role of the protein encoded by the ERBB2 gene?
Answer: A receptor tyrosine kinase involved in cell signaling.
The ERBB2 gene encodes a receptor tyrosine kinase that plays a crucial role in cellular signaling pathways.
Which of the following is NOT listed as a common alias for the HER2 protein?
Answer: EGFR
While HER2 is structurally similar to EGFR (HER1), EGFR itself is a distinct member of the ERBB family and not an alias for HER2.
Why is the protein named HER2?
Answer: Because it is structurally similar to HER1 (EGFR).
The designation HER2 reflects its structural homology to HER1, also known as the Epidermal Growth Factor Receptor (EGFR).
The alias 'Neu' for the HER2 protein originates from which context?
Answer: A rodent glioblastoma cell line.
The alias 'Neu' for HER2 originates from its discovery in a rodent glioblastoma cell line.
What discovery confirmed that HER2, Neu, and ErbB-2 refer to the same gene?
Answer: The molecular cloning of the epidermal growth factor receptor (EGFR).
The molecular cloning of the Epidermal Growth Factor Receptor (EGFR) provided the evidence that HER2, Neu, and ErbB-2 are indeed aliases for the same gene.
On which human chromosome and band is the ERBB2 gene located?
Answer: Chromosome 17, band q12
The ERBB2 gene is located on chromosome 17 at band q12.
Which of the following is NOT a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family that includes HER2?
Answer: HER5 (erbB-5)
The established members of the human ERBB family are EGFR (HER1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4). HER5 is not a recognized member.
Which PDB entry provides structural insight into the interaction between HER2 and Pertuzumab?
Answer: 1s78
PDB entry 1s78 illustrates the structural interaction between HER2 and Pertuzumab.
What does the term 'proto-oncogene' imply about the ERBB2 gene?
Answer: It can contribute to cancer when altered.
The designation 'proto-oncogene' indicates that ERBB2 is a normal gene that has the potential to become an oncogene, contributing to cancer development upon mutation or dysregulation.
What is the function of the ERBB family of receptors?
Answer: Controlling cell growth, differentiation, and survival.
The ERBB family of receptors plays a fundamental role in regulating critical cellular processes, including growth, differentiation, and survival.
The CD designation for proteins like CD340 (HER2) serves what purpose?
Answer: Identifies cell surface markers recognized by antibodies.
The Cluster of Differentiation (CD) designation serves to identify specific cell surface markers that are recognized by antibodies, aiding in cell classification.
What is the enzyme commission (EC) number associated with the protein tyrosine kinase activity of HER2?
Answer: 2.7.10.1
The enzyme commission number 2.7.10.1 is assigned to HER2, denoting its function as a protein tyrosine kinase.
Amplification or over-expression of the ERBB2 gene is typically associated with less aggressive forms of cancer.
Answer: False
Amplification or over-expression of the ERBB2 gene is associated with more aggressive cancer phenotypes, contrary to the assertion of a link with less aggressive forms.
HER2 is a key biomarker and therapeutic target in about 30% of breast cancer cases.
Answer: True
HER2 is a crucial biomarker and therapeutic target in approximately 15% to 30% of breast cancer cases, significantly influencing treatment strategies.
Signaling through the ErbB family generally promotes apoptosis and inhibits cell proliferation.
Answer: False
Signaling mediated by the ErbB family, including HER2, typically promotes cell proliferation and inhibits apoptosis, contributing to cell growth and survival.
ERBB2 gene amplification or over-expression occurs in up to 30% of breast cancer cases.
Answer: True
ERBB2 gene amplification or over-expression is observed in approximately 15% to 30% of breast cancer cases.
HER2 over-expression in breast cancer is linked to a less aggressive disease and a better prognosis.
Answer: False
HER2 over-expression in breast cancer is typically linked to a more aggressive disease course and a poorer prognosis, although targeted therapies have improved outcomes.
HER2 over-expression is exclusively found in breast cancer.
Answer: False
HER2 over-expression is also frequently observed in other cancer types, including ovarian, gastric, and lung adenocarcinomas.
Approximately 7% to 34% of gastric cancer patients exhibit HER2 over-expression.
Answer: True
HER2 over-expression is found in a significant proportion of gastric cancer patients, ranging from approximately 7% to 34%.
HER2 mutations are irrelevant for treatment decisions in non-small-cell lung cancer (NSCLC).
Answer: False
HER2 mutations identified in non-small-cell lung cancers (NSCLC) are clinically relevant and can guide specific treatment decisions for affected patients.
Estrogen receptor signaling normally increases HER2 expression, leading to tamoxifen resistance.
Answer: False
Estrogen receptor signaling typically down-regulates HER2 expression; tamoxifen resistance can arise from complex interactions leading to HER2 upregulation, not from normal ER signaling.
High HER2 copy number amplification in gastric cardia adenocarcinoma is associated with shorter patient survival.
Answer: False
In gastric cardia adenocarcinoma, high HER2 copy number amplification is correlated with a positive contribution to patient survival time.
HER2 over-expression generally opposes apoptosis, contributing to cancer cell survival.
Answer: True
Over-expression of HER2 typically promotes cell proliferation and survival while inhibiting apoptosis, thereby contributing to cancer progression.
What is the consequence of ERBB2 gene amplification or over-expression?
Answer: It plays a role in the development of certain aggressive cancers.
Amplification or over-expression of the ERBB2 gene is a significant factor in the pathogenesis of certain aggressive cancers, promoting uncontrolled cell growth.
In approximately what percentage of breast cancer patients is HER2 a crucial biomarker and therapeutic target?
Answer: Around 15-30%
HER2 is a critical biomarker and therapeutic target in approximately 15% to 30% of breast cancer cases, significantly influencing treatment strategies.
What is the general biological effect of ErbB family signaling, including HER2?
Answer: Inhibits apoptosis and promotes cell proliferation.
Signaling through the ErbB family receptors, including HER2, generally promotes cell proliferation and inhibits apoptosis, contributing to cellular growth and survival.
HER2 over-expression is associated with which characteristic in breast cancer?
Answer: A more aggressive disease course and poorer prognosis.
HER2 over-expression in breast cancer is typically linked to a more aggressive disease course and a poorer prognosis, although targeted therapies have improved outcomes.
Besides breast cancer, HER2 over-expression is commonly found in which other cancer type?
Answer: Ovarian cancer
HER2 over-expression is frequently observed in several other cancer types, including ovarian cancer, gastric cancer, and lung adenocarcinoma.
What is the significance of HER2 amplification in gastric cardia adenocarcinoma, according to the source?
Answer: It may be associated with a positive contribution to survival.
In gastric cardia adenocarcinoma, high HER2 amplification is associated with a positive contribution to patient survival time.
HER2 is activated primarily by direct binding of specific ligands to its extracellular domain.
Answer: False
HER2 activation is primarily ligand-independent, occurring through dimerization with other ERBB family members, unlike other receptors in the family that are activated by direct ligand binding.
HER2 activation primarily occurs through homodimerization or heterodimerization with other ERBB family members.
Answer: True
HER2 activation is initiated by its dimerization, forming either homodimers with itself or heterodimers with other members of the ERBB family.
The primary intracellular pathways activated by HER2 dimerization include the MAPK and PI3K/Akt pathways.
Answer: True
HER2 dimerization triggers downstream signaling cascades, notably including the MAPK and PI3K/Akt pathways, which regulate cell proliferation and survival.
Dimerization of HER2 leads to autophosphorylation and initiates downstream signaling cascades.
Answer: True
Dimerization of HER2, whether homo- or heterodimerization, induces autophosphorylation of its intracellular tyrosine kinase domain, thereby initiating downstream signaling pathways.
HER2 signaling is known to inhibit the MAPK cascade.
Answer: False
HER2 signaling activates, rather than inhibits, the MAPK cascade, a crucial pathway for cell proliferation and differentiation.
HER2 heterodimerizes with HER3 and HER4, but not with itself.
Answer: False
HER2 can undergo both homodimerization (with itself) and heterodimerization (with other ERBB family members like HER3 and HER4).
How does HER2 primarily differ from other ERBB family members regarding activation?
Answer: It lacks identified ligands that directly bind for activation.
A key distinction of HER2 is its lack of identified direct ligands, meaning its activation is primarily mediated through dimerization rather than ligand binding.
What mechanism is responsible for activating the HER2 receptor?
Answer: Homodimerization or heterodimerization with other ERBB family members.
HER2 activation is initiated by its dimerization, forming either homodimers with itself or heterodimers with other members of the ERBB family.
Which signaling pathway is NOT typically activated by HER2 dimerization?
Answer: Wnt signaling pathway
While HER2 dimerization activates pathways like MAPK and PI3K/Akt, the Wnt signaling pathway is not typically considered a direct downstream effector of HER2 signaling.
HER2 testing on biopsy samples is primarily used to determine the patient's favorite color.
Answer: False
HER2 testing on biopsy samples is primarily conducted to assess the patient's suitability for HER2-targeted therapies, not for determining personal preferences.
Immunohistochemistry (IHC) and Fluorescence in situ hybridisation (FISH) are the main methods for HER2 testing.
Answer: True
Immunohistochemistry (IHC) and Fluorescence in situ hybridisation (FISH) are the principal diagnostic methods employed for assessing HER2 status.
An IHC score of 0 for HER2 indicates a positive result requiring Trastuzumab therapy.
Answer: False
An IHC score of 0 for HER2 indicates a negative result and does not warrant Trastuzumab therapy; a score of 3+ is considered positive.
FISH testing measures the amount of HER2 protein present on the cell surface.
Answer: False
FISH (Fluorescence in situ hybridisation) testing measures the gene copy number of ERBB2, whereas IHC measures the protein expression level.
A HER2/CEP17 ratio of 2.0 or higher is considered positive for HER2 amplification by FISH.
Answer: True
A HER2/CEP17 ratio of 2.0 or higher, as determined by FISH, indicates amplification of the HER2 gene.
Measuring serum HER2 levels is the most reliable method for determining eligibility for Trastuzumab therapy.
Answer: False
While serum HER2 levels may offer predictive information, biopsy-based testing (IHC/FISH) remains the standard and most reliable method for determining eligibility for Trastuzumab therapy.
A HER2 IHC score of 1+ is considered positive and warrants Trastuzumab therapy.
Answer: False
An IHC score of 1+ for HER2 is generally considered negative and does not typically warrant Trastuzumab therapy; a score of 3+ is considered positive.
What is the primary purpose of HER2 testing on breast biopsy samples?
Answer: To assess suitability for HER2-targeted therapies.
HER2 testing on biopsy samples is essential for determining patient eligibility for HER2-targeted therapies, as treatment efficacy is dependent on HER2 status.
Which diagnostic method measures the gene copy number of HER2?
Answer: Fluorescence in situ hybridisation (FISH)
Fluorescence in situ hybridisation (FISH) is the diagnostic method used to quantify the gene copy number of ERBB2.
According to the source, what IHC score is considered borderline or equivocal for HER2 expression?
Answer: 2+
An IHC score of 2+ is considered borderline or equivocal for HER2 expression, typically necessitating further confirmation with FISH.
What does a HER2/CEP17 ratio of 2.0 or greater indicate when assessed by FISH?
Answer: HER2 amplification is present.
A HER2/CEP17 ratio of 2.0 or higher, as determined by FISH, indicates amplification of the HER2 gene.
What does a HER2 IHC score of 3+ typically signify?
Answer: Strong, complete circumferential membrane staining.
An IHC score of 3+ for HER2 indicates strong, complete circumferential membrane staining, signifying a positive result for HER2 protein over-expression.
Trastuzumab (Herceptin) is a monoclonal antibody used to treat HER2-positive cancers.
Answer: True
Trastuzumab (Herceptin) is a cornerstone monoclonal antibody therapy specifically employed for the treatment of HER2-positive cancers.
Trastuzumab therapy is effective in all cancer patients, regardless of HER2 status.
Answer: False
Trastuzumab is effective only in cancers where the HER2 protein is over-expressed or amplified, meaning the cancer is classified as HER2-positive.
The standard duration for Trastuzumab therapy in HER2-positive breast cancer is typically one year.
Answer: True
The standard recommended duration for Trastuzumab therapy in HER2-positive breast cancer is one year.
Pertuzumab targets HER2 by blocking its ligand-binding site.
Answer: False
Pertuzumab targets HER2 by inhibiting its dimerization with other receptors, rather than by blocking the ligand-binding site.
Lapatinib and Neratinib are examples of antibody-drug conjugates used for HER2 therapy.
Answer: False
Lapatinib and Neratinib are tyrosine kinase inhibitors (TKIs), not antibody-drug conjugates (ADCs). ADCs used in HER2 therapy include agents like ado-trastuzumab emtansine.
Antibody-drug conjugates deliver cytotoxic drugs directly to cancer cells by targeting HER2.
Answer: True
Antibody-drug conjugates (ADCs) employ an antibody targeting HER2 to deliver a potent cytotoxic payload directly to HER2-expressing cancer cells, minimizing systemic toxicity.
Trastuzumab therapy causes a decrease in the cell cycle inhibitor p27.
Answer: False
Trastuzumab therapy leads to an increase in the cell cycle inhibitor p27, not a decrease.
Pertuzumab inhibits HER2 signaling by preventing its dimerization with other receptors.
Answer: True
Pertuzumab functions by binding to HER2 and preventing its dimerization with other ERBB family receptors, thereby disrupting downstream signaling.
Tyrosine kinase inhibitors like Lapatinib block the extracellular ligand-binding domain of HER2.
Answer: False
Tyrosine kinase inhibitors such as Lapatinib function by blocking the intracellular kinase domain of HER2, not its extracellular ligand-binding domain.
What is the primary therapeutic antibody used against HER2-positive cancers?
Answer: Trastuzumab
Trastuzumab (Herceptin) is the primary monoclonal antibody utilized for therapeutic intervention in HER2-positive cancers.
For which condition is Trastuzumab therapy specifically indicated?
Answer: Cancers where HER2 protein is over-expressed or amplified.
Trastuzumab therapy is indicated specifically for cancers exhibiting HER2 protein over-expression or gene amplification, classifying them as HER2-positive.
What is the typical recommended duration for Trastuzumab therapy in HER2-positive breast cancer?
Answer: 1 year
The standard recommended duration for Trastuzumab therapy in HER2-positive breast cancer is one year.
How does Pertuzumab target HER2?
Answer: By inhibiting HER2 dimerization with other receptors.
Pertuzumab functions by binding to HER2 and preventing its dimerization with other ERBB family receptors, thereby disrupting downstream signaling.
Which of the following are classified as tyrosine kinase inhibitors targeting HER2?
Answer: Lapatinib and Neratinib
Lapatinib and Neratinib are examples of small molecule tyrosine kinase inhibitors that target the intracellular kinase domain of HER2.
What is the therapeutic strategy behind antibody-drug conjugates (ADCs) like ado-trastuzumab emtansine?
Answer: To deliver a cytotoxic drug directly to HER2-expressing cancer cells.
Antibody-drug conjugates (ADCs) employ an antibody targeting HER2 to deliver a potent cytotoxic payload directly to HER2-expressing cancer cells, minimizing systemic toxicity.
What is the role of p27 in response to Trastuzumab therapy, according to the source?
Answer: It increases, acting as a cell cycle inhibitor.
Trastuzumab therapy is associated with an increase in p27 levels, which functions as a cell cycle inhibitor, thereby contributing to the cessation of cell proliferation.
Which of these is an example of a tyrosine kinase inhibitor used to target HER2?
Answer: Tucatinib
Tucatinib is a potent tyrosine kinase inhibitor specifically designed to target HER2.
Which of these is an example of an antibody-drug conjugate used in HER2-targeted therapy?
Answer: Trastuzumab deruxtecan
Trastuzumab deruxtecan is an antibody-drug conjugate that utilizes an antibody targeting HER2 to deliver a cytotoxic payload.